Journal articles: 'Conserved region'

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Martinez-Porchas, Marcel, Enrique Villalpando-Canchola, Luis Enrique Ortiz Suarez, and Francisco Vargas-Albores. "How conserved are the conserved 16S-rRNA regions?" PeerJ 5 (February 28, 2017): e3036. http://dx.doi.org/10.7717/peerj.3036.

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The 16S rRNA gene has been used as master key for studying prokaryotic diversity in almost every environment. Despite the claim of several researchers to have the best universal primers, the reality is that no primer has been demonstrated to be truly universal. This suggests that conserved regions of the gene may not be as conserved as expected. The aim of this study was to evaluate the conservation degree of the so-called conserved regions flanking the hypervariable regions of the 16S rRNA gene. Data contained in SILVA database (release 123) were used for the study. Primers reported as matches of each conserved region were assembled to form contigs; sequences sizing 12 nucleotides (12-mers) were extracted from these contigs and searched into the entire set of SILVA sequences. Frequency analysis shown that extreme regions, 1 and 10, registered the lowest frequencies. 12-mer frequencies revealed segments of contigs that were not as conserved as expected (≤90%). Fragments corresponding to the primer contigs 3, 4, 5b and 6a were recovered from all sequences in SILVA database. Nucleotide frequency analysis in each consensus demonstrated that only a small fraction of these so-called conserved regions is truly conserved in non-redundant sequences. It could be concluded that conserved regions of the 16S rRNA gene exhibit considerable variation that has to be considered when using this gene as biomarker.

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Xiao, Ming, Huaibo Li, Yujing Wang, Xiaohui Wang, Wei Wang, Jun Peng, Jiakuan Chen, and Bo Li. "Characterization of the N-terminal domain of classical swine fever virus RNA-dependent RNA polymerase." Journal of General Virology 87, no. 2 (February 1, 2006): 347–56. http://dx.doi.org/10.1099/vir.0.81385-0.

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To investigate RNA-dependent RNA polymerase (RdRp) further, mutational analysis of the N-terminal domain of the NS5B protein of Classical swine fever virus was performed. Results show that the N-terminal domain (positions 1–300) of the protein might be divided artificially into four different regions, N1–N4. The N1 region (positions 1–61) contained neither conserved lysine nor conserved arginine residues. NS5B protein with deletion of the N1 region has the capacity for elongative RNA synthesis, but not for de novo RNA synthesis on natural templates. All substitutions of the conserved lysines and arginines in the N2 region (positions 63–216) destroyed RdRp activity completely. Substitutions of the conserved arginines in the N3 region (positions 217–280) seriously reduced RdRp activity. However, all substitutions of the conserved lysines in this region enhanced RNA synthesis and made the mutants synthesize RNA on any template. Substitutions of the conserved arginines in the N4 region (positions 281–300) reduced elongative synthesis and destroyed de novo RNA synthesis. In contrast, substitutions of lysines in this region did not affect RdRp activity significantly. These data indicate that the N3 region might be related to the enzymic specificity for templates, and the conserved lysines and arginines in different regions have different effects on RdRp activity. In combination with the published crystal structure of bovine viral diarrhea virus NS5B, these results define the important role of the N-terminal domain of NS5B for template recognition and de novo RNA synthesis.

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Hwang, Ying T., Harmon J. Zuccola, Qiaosheng Lu, and Charles B. C. Hwang. "A Point Mutation within Conserved Region VI of Herpes Simplex Virus Type 1 DNA Polymerase Confers Altered Drug Sensitivity and Enhances Replication Fidelity." Journal of Virology 78, no. 2 (January 15, 2004): 650–57. http://dx.doi.org/10.1128/jvi.78.2.650-657.2004.

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ABSTRACT Herpes simplex virus type 1 (HSV-1) DNA polymerase contains several conserved regions within the polymerase domain. The conserved regions I, II, III, V, and VII have been shown to have functional roles in the interaction with deoxynucleoside triphosphates (dNTPs) and DNA. However, the role of conserved region VI in DNA replication has remained unclear due, in part, to the lack of a well-characterized region VI mutant. In this report, recombinant viruses containing a point mutation (L774F) within the conserved region VI were constructed. These recombinant viruses were more susceptible to aphidicolin and resistant to both foscarnet and acyclovir, compared to the wild-type KOS strain. Marker transfer experiments demonstrated that the L774F mutation conferred the altered drug sensitivities. Furthermore, mutagenesis assays demonstrated that L774F recombinant viruses containing the supF marker gene, which was integrated within the thymidine kinase locus (tk), exhibited increased fidelity of DNA replication. These data indicate that conserved region VI, together with other conserved regions, forms the polymerase active site, has a role in the interaction with deoxyribonucleotides, and regulates DNA replication fidelity. The possible effect of the L774F mutation in altering the polymerase structure and activity is discussed.

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Kontinen, V. P., M. Yamanaka, K. i. Nishiyama, and H. Tokuda. "Roles of the Conserved Cytoplasmic Region and Non-Conserved Carboxy-Terminal Region of SecE in Escherichia coli Protein Translocase." Journal of Biochemistry 119, no. 6 (June 1, 1996): 1124–30. http://dx.doi.org/10.1093/oxfordjournals.jbchem.a021358.

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Wong, H. K., and E. B. Ziff. "Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters." Journal of Virology 68, no. 8 (1994): 4910–20. http://dx.doi.org/10.1128/jvi.68.8.4910-4920.1994.

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Paku, Keum Soon, Yu Umenaga, Tsunego Usui, Ai Fukuyo, Atsuo Mizuno, Yasuko In, Toshimasa Ishida, and Koji Tomoo. "A conserved motif within the flexible C-terminus of the translational regulator 4E-BP is required for tight binding to the mRNA cap-binding protein eIF4E." Biochemical Journal 441, no. 1 (December 14, 2011): 237–45. http://dx.doi.org/10.1042/bj20101481.

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Although the central α-helical Y(X)4LΦ motif (X, variable amino acid; Φ, hydrophobic amino acid) of the translational regulator 4E-BP [eIF (eukaryotic initiation factor) 4E-binding protein] is the core binding region for the mRNA cap-binding protein eIF4E, the functions of its N- and C-terminal flexible regions for interaction with eIF4E remain to be elucidated. To identify the role for the C-terminal region in such an interaction, the binding features of full-length and sequential C-terminal deletion mutants of 4E-BPn (n=1–3) subtypes were investigated by SPR (surface plasmon resonance) analysis and ITC (isothermal titration calorimetry). Consequently, the conserved PGVTS/T motif within the C-terminal region was shown to act as the second binding region and to play an important role in the tight binding to eIF4E. The 4E-BP subtypes increased the association constant with eIF4E by approximately 1000-fold in the presence of this conserved region compared with that in the absence of this region. The sequential deletion of this conserved region in 4E-BP1 showed that deletion of Val81 leads to a considerable decrease in the binding ability of 4E-BP. Molecular dynamics simulation suggested that the conserved PGVTS/T region functions as a kind of paste, adhering the root of both the eIF4E N-terminal and 4E-BP C-terminal flexible regions through a hydrophobic interaction, where valine is located at the crossing position of both flexible regions. It is concluded that the conserved PGVTS/T motif within the flexible C-terminus of 4E-BP plays an auxiliary, but indispensable, role in strengthening the binding of eIF4E to the core Y(X)4LΦ motif.

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Hsu, Hsin-Hsien, Wei-Cheng Huang, Jia-Perng Chen, Liang-Yin Huang, Chai-Fong Wu, and Ban-Yang Chang. "Properties of Bacillus subtilis σA Factors with Region 1.1 and the Conserved Arg-103 at the N Terminus of Region 1.2 Deleted." Journal of Bacteriology 186, no. 8 (April 15, 2004): 2366–75. http://dx.doi.org/10.1128/jb.186.8.2366-2375.2004.

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ABSTRACT σ factors in the σ70 family can be classified into the primary and alternative σ factors according to their physiological functions and amino acid sequence similarities. The primary σ factors are composed of four conserved regions, with the conserved region 1 being divided into two subregions. Region 1.1, which is absent from the alternative σ factor, is poor in conservation; however, region 1.2 is well conserved. We investigated the importance of these two subregions to the function of Bacillus subtilis σA, which belongs to a subgroup of the primary σ factor lacking a 254-amino-acid spacer between regions 1 and 2. We found that deletion of not more than 100 amino acid residues from the N terminus of σA, which removed part or all region 1.1, did not affect the overall transcription activity of the truncated σA-RNA polymerase in vitro, indicating that region 1.1 is not required for the functioning of σA in RNA polymerase holoenzyme. This finding is consistent with the complementation data obtained in vivo. However, region 1.1 is able to negatively modulate the promoter DNA-binding activity of the σA-RNA polymerase. Further deletion of the conserved Arg-103 at the N terminus of region 1.2 increased the content of stable secondary structures of the truncated σA and greatly reduced the transcription activity of the truncated σA-RNA polymerase by lowering the efficiency of transcription initiation after core binding of σA. More importantly, the conserved Arg-103 was also demonstrated to be critical for the functioning of the full-length σA in RNA polymerase.

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Tobar, H. F., P. A. Moreno, and P. E. Velez. "Highly conserved regions in the 5’ region of human olfactory receptor genes." Genetics and Molecular Research 8, no. 1 (2009): 117–28. http://dx.doi.org/10.4238/vol8-1gmr550.

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., Usman Sumo Friend Ta, Herbert Wybert Butar ., Radya Umbas ., and Zulfa Hidayah . "Conserved Region Analysis of Oncogenic Human Papillomavirus Genome." Biotechnology(Faisalabad) 6, no. 1 (December 15, 2006): 93–96. http://dx.doi.org/10.3923/biotech.2007.93.96.

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10

Cihlar, Tomas, Michael D. Fuller, and Julie M. Cherrington. "Characterization of Drug Resistance-Associated Mutations in the Human Cytomegalovirus DNA Polymerase Gene by Using Recombinant Mutant Viruses Generated from Overlapping DNA Fragments." Journal of Virology 72, no. 7 (July 1, 1998): 5927–36. http://dx.doi.org/10.1128/jvi.72.7.5927-5936.1998.

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ABSTRACT A number of specific point mutations in the human cytomegalovirus (HCMV) DNA polymerase (UL54) gene have been tentatively associated with decreased susceptibility to antiviral agents and consequently with clinical failure. To precisely determine the roles of UL54 mutations in HCMV drug resistance, recombinant UL54 mutant viruses were generated by using cotransfection of nine overlapping HCMV DNA fragments into permissive fibroblasts, and their drug susceptibility profiles were determined. Amino acid substitutions located in UL54 conserved region IV (N408D, F412C, and F412V), region V (A987G), and δ-region C (L501I, K513E, P522S, and L545S) conferred various levels of resistance to cidofovir and ganciclovir. Mutations in region II (T700A and V715M) and region VI (V781I) were associated with resistance to foscarnet and adefovir. The region II mutations also conferred moderate resistance to lobucavir. In contrast to mutations in other UL54 conserved regions, those residing specifically in region III (L802M, K805Q, and T821I) were associated with various drug susceptibility profiles. Mutations located outside the known UL54 conserved regions (S676G and V759M) did not confer any significant changes in HCMV drug susceptibility. Predominantly an additive effect of multiple UL54 mutations with respect to the final drug resistance phenotype was demonstrated. Finally, the influence of selected UL54 mutations on the susceptibility of viral DNA replication to antiviral drugs was characterized by using a transient-transfection-plus-infection assay. Results of this work exemplify specific roles of the UL54 conserved regions in the development of HCMV drug resistance and may help guide optimization of HCMV therapy.

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Yang, Otto O., Ayub Ali, Noriyuki Kasahara, Emmanuelle Faure-Kumar, Jin Young Bae, Louis J. Picker, and Haesun Park. "Short Conserved Sequences of HIV-1 Are Highly Immunogenic and Shift Immunodominance." Journal of Virology 89, no. 2 (November 5, 2014): 1195–204. http://dx.doi.org/10.1128/jvi.02370-14.

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ABSTRACTCellular immunity is pivotal in HIV-1 pathogenesis but is hampered by viral sequence diversity. An approach to minimize this diversity is to focus immunity on conserved proteome sequences; therefore, we selected four relatively conserved regions (Gag amino acids 148 to 214 and 250 to 335, Env amino acids 521 to 606, and Nef amino acids 106 to 148), each created in three mosaics, to provide better coverage of M-group HIV-1 sequences. A conserved-region vaccine (CRV) delivering genes for these four regions as equal mixtures of three mosaics each (each region at a separate injection site) was compared to a whole-protein vaccine (WPV) delivering equimolar amounts of genes for whole Gag, Env, and Nef as clade B consensus sequences (separate injection sites). Three rhesus macaques were vaccinated via three DNA primes and a recombinant adenovirus type 5 boost (weeks 0, 4, 8, and 24, respectively). Although CRV inserts were about one-fifth that of WPV, the CRV generated comparable-magnitude blood CD4+and CD8+T lymphocyte responses against Gag, Env, and Nef. WPV responses preferentially targeted proteome areas outside the selected conserved regions in direct proportion to sequence lengths, indicating similar immunogenicities for the conserved regions and the outside regions. The CRV yielded a conserved-region targeting density that was approximately 5-fold higher than that of the WPV. A similar pattern was seen for bronchoalveolar lymphocytes, but with quadruple the magnitudes seen in blood. Overall, these findings demonstrate that the selected conserved regions are highly immunogenic and that anatomically isolated vaccinations with these regions focus immunodominance compared to the case for full-length protein vaccination.IMPORTANCEHIV-1 sequence diversity is a major barrier limiting the capability of cellular immunity to contain infection and the ability of vaccines to match circulating viral sequences. To date, vaccines tested in humans have delivered whole proteins or genes for whole proteins, and it is unclear whether including only conserved sequences would yield sufficient cellular immunogenicity. We tested a vaccine delivering genes for four small conserved HIV-1 regions compared to a control vaccine with genes for whole Gag, Env, and Nef. Although the conserved regions ranged from 43 to 86 amino acids and comprised less than one-fifth of the whole Gag/Env/Nef sequence, the vaccines elicited equivalent total magnitudes of both CD4+and CD8+T lymphocyte responses. These data demonstrate the immunogenicity of these small conserved regions and the potential for a vaccine to steer immunodominance toward conserved epitopes.

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Hansen, Johanna K., Karen P. Demick, John M. Mansfield, and Katrina T. Forest. "Conserved Regions from Neisseria gonorrhoeae Pilin Are Immunosilent and Not Immunosuppressive." Infection and Immunity 75, no. 8 (June 11, 2007): 4138–47. http://dx.doi.org/10.1128/iai.02015-06.

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ABSTRACT PilE is the primary subunit of type IV pili from Neisseria gonorrhoeae and contains a surface-exposed hypervariable region thought to be one feature of pili that has prevented development of a pilin-based vaccine. We have created a three-dimensional structure-based antigen by replacing the hypervariable region of PilE with an aspartate-glutamine linker chosen from the sequence of Pseudomonas aeruginosa PilA. We then characterized murine immune responses to this novel protein to determine if conserved PilE regions could serve as a vaccine candidate. The control PilE protein elicited strong T-cell-dependent B-cell responses that are specific to epitopes in both the hypervariable deletion and control proteins. In contrast, the hypervariable deletion protein was unable to elicit an immune response in mice, suggesting that in the absence of the hypervariable region, the conserved regions of PilE alone are not sufficient for antibody production. Further analysis of these PilE proteins with suppressor cell assays showed that neither suppresses T- or B-cell responses, and flow cytometry experiments suggested that they do not exert suppressor effects by activating T regulatory cells. Our results show that in the murine model, the hypervariable region of PilE is required to activate immune responses to pilin, whereas the conserved regions are unusually nonimmunogenic. In addition, we show that both hypervariable and conserved regions of pilin are not suppressive, suggesting that PilE does not cause the decrease in T-cell populations observed during gonococcal cervicitis.

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Prasad, Shiv S., Terence V. Starr, and Ann M. Rose. "Molecular characterization in the dpy-14 region identifies the S-adenosylhomocysteine hydrolase gene in Caenorhabditis elegans." Genome 36, no. 1 (February 1, 1993): 57–65. http://dx.doi.org/10.1139/g93-008.

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The region around dpy-14 on chromosome 1 of Caenorhabditis elegans has been extensively studied genetically, with regard to essential gene organization. This region was one of the first for which cloned DNA was available as a result of restriction fragment length polymorphism mapping. To examine the information content of the cloned DNA in this region, evolutionarily conserved sequences were identified by cross-species hybridization. Ten regions of conservation have been identified and characterized with regard to mRNA abundance and DNA sequence. cDNAs were obtained for seven of these conserved regions and sequence from the cDNAs were used to search the SWISS protein and EMBL nucleotide data banks. Two coding regions shared DNA identities with existing sequences, the opa repeat family of Drosophila and the S-adenosylhomocysteine hydrolase gene. Of the three for which no corresponding cDNA were found, one corresponds to the snRNA U1-1. The other two did not detect transcripts on Northern analysis and are either conserved, but not coding, or code for low abundance transcripts. The density of conserved coding regions in this study was one per 15 kbp of genomic DNA, three times lower than that reported on chromosome 3 by the genome sequencing project.Key words: Caenorhabditis elegans, coding regions, genome, S-adenosylhomocysteine.

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Archambault, Jacques, David B. Jansma, Jean H. Kawasoe, Kim T. Arndt, Jack Greenblatt, and James D. Friesen. "Stimulation of Transcription by Mutations Affecting Conserved Regions of RNA Polymerase II." Journal of Bacteriology 180, no. 10 (May 15, 1998): 2590–98. http://dx.doi.org/10.1128/jb.180.10.2590-2598.1998.

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ABSTRACT Mutations that increase the low-level transcription of theSaccharomyces cerevisiae HIS4 gene, which results from deletion of the genes encoding transcription factors BAS1, BAS2, and GCN4, were isolated previously in SIT1 (also known asRPO21, RPB1, and SUA8), the gene encoding the largest subunit of RNA polymerase II (RNAPII). Here we show that sit1 substitutions cluster in two conserved regions of the enzyme which form part of the active site. Sixsit1 mutations, affect region F, a region that is involved in transcriptional elongation and in resistance to α-aminatin. Foursit1 substitutions lie in another region involved in transcriptional elongation, region D, which binds Mg2+ ions essential for RNA catalysis. One region D substitution is lethal unless suppressed by a substitution in region G and interacts genetically withPPR2, the gene encoding transcription elongation factor IIS. Some sit1 substitutions affect the selection of transcriptional start sites at the CYC1 promoter in a manner reminiscent of that of sua8 (sua stands for suppression of upstream ATG) mutations. Together with previous findings which indicate that regions D and G are in close proximity to the 3′ end of the nascent transcript and that region F is involved in the translocation process, our results suggest that transcriptional activation by the sit1 mutations results from alteration of the RNAPII active center.

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REDDY, BOOJALA V. B., and YIANNIS N. KAZNESSIS. "A QUANTITATIVE ANALYSIS OF INTERFACIAL AMINO ACID CONSERVATION IN PROTEIN-PROTEIN HETERO COMPLEXES." Journal of Bioinformatics and Computational Biology 03, no. 05 (October 2005): 1137–50. http://dx.doi.org/10.1142/s0219720005001429.

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A long-standing question in molecular biology is whether interfaces of protein-protein complexes are more conserved than the rest of the protein surfaces. Although it has been reported that conservation can be used as an indicator for predicting interaction sites on proteins, there are recent reports stating that the interface regions are only slightly more conserved than the rest of the protein surfaces, with conservation signals not being statistically significant enough for predicting protein-protein binding sites. In order to properly address these controversial reports we have studied a set of 28 well resolved hetero complex structures of proteins that consists of transient and non-transient complexes. The surface positions were classified into four conservation classes and the conservation index of the surface positions was quantitatively analyzed. The results indicate that the surface density of highly conserved positions is significantly higher in the protein-protein interface regions compared with the other regions of the protein surface. However, the average conservation index of the patches in the interface region is not significantly higher compared with other surface regions of the protein structures. This finding demonstrates that the number of conserved residue positions is a more appropriate indicator for predicting protein-protein binding sites than the average conservation index in the interacting region. We have further validated our findings on a set of 59 benchmark complex structures. Furthermore, an analysis of 19 complexes of antigen-antibody interactions shows that there is no conservation of amino acid positions in the interacting regions of these complexes, as expected, with the variable region of the immunoglobulins interacting mostly with the antigens. Interestingly, antigen interacting regions also have a higher number of non-conserved residue positions in the interacting region than the rest of the protein surface.

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Kim, G. J., and H. S. Kim. "Identification of the structural similarity in the functionally related amidohydrolases acting on the cyclic amide ring." Biochemical Journal 330, no. 1 (February 15, 1998): 295–302. http://dx.doi.org/10.1042/bj3300295.

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The functionally related amidohydrolases, including D-hydantoinases, dihydropyrimidinases, allantoinases and dihydro-orotases, share a similar catalytic function of acting on the cyclic amide ring. We aligned 16 amidohydrolases by taking account of the conservative substitution and found a number of highly conserved regions and invariant amino acid residues. Analyses of the secondary structure and hydropathy profile of the enzymes revealed a significant degree of similarity in the conserved regions. Among the regions, the long stretched region I is of particular interest, because it is mainly composed of invariant amino acid residues, showing a similarity of 69% for the enzymes. A search of the protein data bank using the sequence of the conserved region I identified a number of proteins possessing a similar catalytic property, providing a clue that this region might be linked with the catalytic function. As a particular sequence, one aspartic acid and four histidine residues are found to be rigidly conserved in the functionally related amidohydrolases. In order to investigate the significance of the conserved residues, site-directed mutagenesis was carried out typically for the D-hydantoinase gene cloned from Bacillus stearothermophilus SD1. These residues were found to be essential for metal binding as well as catalysis, strongly implying that these invariant residues play a critical role in other enzymes as well as in D-hydantoinase. On the basis of the similar catalytic function and existence of the rigidly conserved sequence, we propose a close evolutionary relationship among the functionally related amidohydrolases, including D-hydantoinase, dihydropyrimidinase, allantoinase and dihydro-orotase.

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Pacin-Ruiz, Beatriz, María Francesca Cortese, David Tabernero, Sara Sopena, Josep Gregori, Selene García-García, Rosario Casillas, et al. "Inspecting the Ribozyme Region of Hepatitis Delta Virus Genotype 1: Conservation and Variability." Viruses 14, no. 2 (January 22, 2022): 215. http://dx.doi.org/10.3390/v14020215.

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The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved regions potentially suitable for a gene-silencing strategy. HDV RNA was extracted from 2 longitudinal samples of chronic HDV patients and the ribozyme (nucleotide, nt 688–771) was analyzed using NGS. QS conservation, variability and genetic distance were analyzed. Mutations were identified by aligning sequences with their specific genotype consensus. The main relevant mutations were tested in vitro. The ribozyme was conserved overall, with a hyper-conserved region between nt 715–745. No difference in QS was observed over time. The most variable region was between nt 739–769. Thirteen mutations were observed, with three showing a higher frequency: T23C, T69C and C64 deletion. This last strongly reduced HDV replication by more than 1 log in vitro. HDV Ribozyme QS was generally highly conserved and was maintained during follow-up. The most conserved portion may be a valuable target for a gene-silencing strategy. The presence of the C64 deletion may strongly impair viral replication, as it is a potential mechanism of viral persistence.

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Wilkerson, C. G., S. M. King, and G. B. Witman. "Molecular analysis of the gamma heavy chain of Chlamydomonas flagellar outer-arm dynein." Journal of Cell Science 107, no. 3 (March 1, 1994): 497–506. http://dx.doi.org/10.1242/jcs.107.3.497.

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We report here the complete sequence of the gamma dynein heavy chain of the outer arm of the Chlamydomonas flagellum, and partial sequences for six other dynein heavy chains. The gamma dynein heavy chain sequence contains four P-loop motifs, one of which is the likely hydrolytic site based on its position relative to a previously mapped epitope. Comparison with available cytoplasmic and flagellar dynein heavy chain sequences reveals regions that are highly conserved in all dynein heavy chains sequenced to date, regions that are conserved only among axonemal dynein heavy chains, and regions that are unique to individual dynein heavy chains. The presumed hydrolytic site is absolutely conserved among dyneins, two other P loops are highly conserved among cytoplasmic dynein heavy chains but not in axonemal dynein heavy chains, and the fourth P loop is invariant in axonemal dynein heavy chains but not in cytoplasmic dynein. One region that is very highly conserved in all dynein heavy chains is similar to a portion of the ATP-sensitive microtubule-binding domain of kinesin. Two other regions present in all dynein heavy chains are predicted to have high alpha-helical content and have a high probability of forming coiled-coil structures. Overall, the central one-third of the gamma dynein heavy chain is most conserved whereas the N-terminal one-third is least conserved; the fact that the latter region is divergent between the cytoplasmic dynein heavy chain and two different axonemal dynein heavy chains suggests that it is involved in chain-specific functions.

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Kairova, Markhabat, and Gulnara Sitpayeva. "Sequencing conserved region of endangered species Celtis caucasica Willd." BIO Web of Conferences 31 (2021): 00009. http://dx.doi.org/10.1051/bioconf/20213100009.

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The rarest species of relict ironwood C. caucasica Willd. is naturally occurred on the Ile-Alatau Mountains but very little is known about genetic diversity and distribution and size of its populations in Kazakhstan. In during the sampling expedition were found two additional plant populations in Dzungarian and Kyrgyz Alatau Ranges. The objective of this work was targeted towards sequencing ITS region of C. caucasica and compare the obtained nucleotide sequence with available data on NCBI GeneBank for confident species identification. The identity of C. caucasica sequence and available C. australis and C. bungeana sequences was 93.87% and less. It could be associated with absence sequences producing significant alignments with the studied ironwood sequence and important deposited sequences of GenBank lacking Latin binominals is from environmental samples. Clarifying taxonomical status species and subspecies is difficult by morphological data and molecular markers should be used to correct identifying an endangered species of C. caucasica growing in the east-southern and the south regions of Kazakhstan and providing direction to the conservation management of the plant.

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Hanna-Rose, W., J. D. Licht, and U. Hansen. "Two evolutionarily conserved repression domains in the Drosophila Kruppel protein differ in activator specificity." Molecular and Cellular Biology 17, no. 8 (August 1997): 4820–29. http://dx.doi.org/10.1128/mcb.17.8.4820.

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To identify biologically functional regions in the product of the Drosophila melanogaster gene Kruppel, we cloned the Kruppel homolog from Drosophila virilis. Both the previously identified amino (N)-terminal repression region and the DNA-binding region of the D. virilis Kruppel protein are greater than 96% identical to those of the D. melanogaster Kruppel protein, demonstrating a selective pressure to maintain the integrity of each region during 60 million to 80 million years of evolution. An additional region in the carboxyl (C) terminus of Kruppel that was most highly conserved was examined further. A 42-amino-acid stretch within the conserved C-terminal region also encoded a transferable repression domain. The short, C-terminal repression region is a composite of three subregions of distinct amino acid composition, each containing a high proportion of either basic, proline, or acidic residues. Mutagenesis experiments demonstrated, unexpectedly, that the acidic residues contribute to repression function. Both the N-terminal and C-terminal repression regions were tested for the ability to affect transcription mediated by a variety of activator proteins. The N-terminal repression region was able to inhibit transcription in the presence of multiple activators. However, the C-terminal repression region inhibited transcription by only a subset of the activator proteins. The different activator specificities of the two regions suggest that they repress transcription by different mechanisms and may play distinct biological roles during Drosophila development.

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Ali, Ramzan, and Muhammad Imtiaz Shafiq. "Sequence, Structure, and Binding Analysis of Cyclodextrinase (TK1770) fromT. kodakarensis(KOD1) Using anIn SilicoApproach." Archaea 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/179196.

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Thermostable cyclodextrinase (Tk1770 CDase) from hyperthermophilic archaeonThermococcus kodakarensis(KOD1) hydrolyzes cyclodextrins into linear dextrins. The sequence of Tk1770 CDase retrieved from UniProt was aligned with sequences of sixteen CD hydrolyzing enzymes and a phylogenetic tree was constructed using Bayesian inference. The homology model of Tk1770 CDase was constructed and optimized with Modeller v9.14 program. The model was validated with ProSA server and PROCHECK analysis. Four conserved regions and the catalytic triad consisting of Asp411, Glu437, and Asp502 of GH13 family were identified in catalytic site. Also an additional fifth conserved region downstream to the fourth region was also identified. The structure of Tk1770 CDase consists of an additional N′-domain and a helix-loop-helix motif that is conserved in all archaeal CD hydrolyzing enzymes. The N′-domain contains an extended loop region that forms a part of catalytic domain and plays an important role in stability and substrate binding. The docking of substrate into catalytic site revealed the interactions with different conserved residues involved in substrate binding and formation of enzyme-substrate complex.

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Helt, Anna-Marija, and Denise A. Galloway. "Destabilization of the Retinoblastoma Tumor Suppressor by Human Papillomavirus Type 16 E7 Is Not Sufficient To Overcome Cell Cycle Arrest in Human Keratinocytes." Journal of Virology 75, no. 15 (August 1, 2001): 6737–47. http://dx.doi.org/10.1128/jvi.75.15.6737-6747.2001.

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ABSTRACT The E7 oncoprotein of human papillomavirus type 16 promotes cell proliferation in the presence of antiproliferative signals. Mutagenesis of E7 has revealed that this activity requires three regions, conserved regions 1 and 2 and a C-terminal zinc finger. Binding to the retinoblastoma tumor repressor (Rb) through an LxCxE motif in conserved region 2 is necessary, but not sufficient, for E7 to induce proliferation. We tested the hypothesis that binding to Rb is not sufficient because conserved region 1 and/or the C terminus are required for E7 to functionally inactivate Rb and thus induce proliferation. One mechanism proposed for how E7 inactivates Rb is by blocking Rb-E2F binding. Either conserved region 1 or the C terminus was necessary, in combination with the LxCxE motif, for E7 to block Rb-E2F binding in vitro. While all full-length E7 proteins with mutations outside of the LxCxE motif inhibited Rb-E2F binding, some failed to abrogate cell cycle arrest, demonstrating that blocking Rb-E2F binding is not sufficient for abrogating antiproliferative signals. Another mechanism proposed for how E7 inactivates Rb is by promoting the destabilization of Rb protein. Mutations in conserved region 1 or the LxCxE motif prevented E7 from reducing the half-life of Rb. Though no specific C-terminal residues of E7 were essential for destabilizing Rb, a novel class of mutations that uncouple the destabilization of Rb from the deregulation of keratinocyte proliferation was discovered. Destabilization of Rb correlated with the abrogation of Rb-induced quiescence but was not sufficient for overriding DNA damage-induced cell cycle arrest or for increasing keratinocyte life span. Finally, the same regions of E7 required for destabilizing Rb were required for reducing p107 and p130 levels. Together, these results suggest that inactivation of all three Rb family members is not sufficient to deregulate keratinocyte cell cycle control.

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Kharisma, Viol Dhea, Arif Nur Muhammad Ansori, Gabrielle Ann Villar Posa, Wahyu Choirur Rizky, Sofy Permana, and Arli Aditya Parikesit. "Conserved B-cell epitope identification of envelope glycoprotein (GP120) HIV-1 to develop multi-strain vaccine candidate through bioinformatics approach." Jurnal Teknologi Laboratorium 10, no. 1 (June 28, 2021): 06–13. http://dx.doi.org/10.29238/teknolabjournal.v10i1.274.

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Acquired immune deficiency syndrome (AIDS) has been identified from US patients since 1981. AIDS is caused by infection with the human immunodeficiency virus type 1 (HIV-1) which is a retrovirus. HIV-1 gp120 can be recognized by the immune system because it is located outside the virion. The conserved region is identified in gp120, and it is recognized by an immune cell which then initiates specific immune responses, viral mutation escape, and increase vaccine protection coverage, a benefit derived from the conserved region-based vaccine design. However, previous researchers have little knowledge on this conserved region as a target for vaccine design. This paper explains how the conserved region of gp120 HIV-1 is a major target for vaccine design through a bioinformatics approach. The conserved region from gp120 was explored as a vaccine design target with a bioinformatics tool that consists of B-cell epitope mapping, vaccine properties, molecular docking, and dynamic simulation. The peptide vaccine candidate of B5 with the gp120 HIV-1 conserved region was found to provoke B-cell activation through a direct pathway, produce specific antibody, and increase protection from multi-strain viral infection.

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Sweeney, R., L. Chen, and M. C. Yao. "An rRNA variable region has an evolutionarily conserved essential role despite sequence divergence." Molecular and Cellular Biology 14, no. 6 (June 1994): 4203–15. http://dx.doi.org/10.1128/mcb.14.6.4203-4215.1994.

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Regions extremely variable in size and sequence occur at conserved locations in eukaryotic rRNAs. The functional importance of one such region was determined by gene reconstruction and replacement in Tetrahymena thermophila. Deletion of the D8 region of the large-subunit rRNA inactivates T. thermophila rRNA genes (rDNA): transformants containing only this type of rDNA are unable to grow. Replacement with an unrelated sequence of similar size or a variable region from a different position in the rRNA also inactivated the rDNA. Mutant rRNAs resulting from such constructs were present only in precursor forms, suggesting that these rRNAs are deficient in either processing or stabilization of the mature form. Replacement with D8 regions from three other organisms restored function, even though the sequences are very different. Thus, these D8 regions share an essential functional feature that is not reflected in their primary sequences. Similar tertiary structures may be the quality these sequences share that allows them to function interchangeably.

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Sweeney, R., L. Chen, and M. C. Yao. "An rRNA variable region has an evolutionarily conserved essential role despite sequence divergence." Molecular and Cellular Biology 14, no. 6 (June 1994): 4203–15. http://dx.doi.org/10.1128/mcb.14.6.4203.

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Regions extremely variable in size and sequence occur at conserved locations in eukaryotic rRNAs. The functional importance of one such region was determined by gene reconstruction and replacement in Tetrahymena thermophila. Deletion of the D8 region of the large-subunit rRNA inactivates T. thermophila rRNA genes (rDNA): transformants containing only this type of rDNA are unable to grow. Replacement with an unrelated sequence of similar size or a variable region from a different position in the rRNA also inactivated the rDNA. Mutant rRNAs resulting from such constructs were present only in precursor forms, suggesting that these rRNAs are deficient in either processing or stabilization of the mature form. Replacement with D8 regions from three other organisms restored function, even though the sequences are very different. Thus, these D8 regions share an essential functional feature that is not reflected in their primary sequences. Similar tertiary structures may be the quality these sequences share that allows them to function interchangeably.

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Walrad, Pegine B., Saiyu Hang, Genevieve S. Joseph, Julia Salas, and J. Peter Gergen. "Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity." Molecular Biology of the Cell 21, no. 13 (July 2010): 2315–26. http://dx.doi.org/10.1091/mbc.e09-11-0953.

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Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators.

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Tsuji, Y., J. Ninomiya-Tsuji, S. V. Torti, and F. M. Torti. "Augmentation by IL-1 alpha of tumor necrosis factor-alpha cytotoxicity in cells transfected with adenovirus E1A." Journal of Immunology 150, no. 5 (March 1, 1993): 1897–907. http://dx.doi.org/10.4049/jimmunol.150.5.1897.

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Abstract The introduction of adenovirus E1A into NIH3T3 mouse fibroblasts renders them susceptible to the cytotoxic action of TNF-alpha. We found that cells transfected with 13S E1A cDNA were not similarly rendered sensitive to IL-1 alpha; however, in cells transfected with 13S E1A cDNA, TNF cytotoxicity was augmented by treatment with IL-1. To understand the role of E1A in the cytotoxic action of these cytokines, several 13S E1A cDNA deletion mutants were constructed, transfected into NIH3T3 cells, and tested for their ability to induce TNF sensitivity in the presence and absence of IL-1. Cells transfected with mutants of 13S E1A with deletions of carboxyl-terminal amino acids 223 to 289 or 151 to 289 (conserved region 3) exhibited a minimal ability to reverse E1A-induced TNF cytotoxicity but a significant ability to reverse IL-1-mediated augmentation of TNF cytotoxicity. Cells transfected with other deletion mutants of 13S E1A, including those with an internal deletion encompassing conserved region 1 (amino acid positions 23 to 107) or a deletion including conserved regions 2 and 3 (amino acid positions 108 to 289), although initially TNF resistant, became TNF sensitive on prolonged exposure to TNF. Cells transfected with these mutants also showed a reduction in IL-1-augmented TNF cytotoxicity. The larger internal deletion of E1A at amino acid positions 23 to 150 (conserved regions 1 and 2), which includes regions important for transformation, transcriptional repression, and association with cellular proteins, resulted in the complete loss of the ability of E1A to induce TNF sensitivity even in the presence of IL-1. Immunoprecipitation experiments showed that E1A proteins in NIH3T3 cells associated with a cellular 115-kDa protein, which did not co-migrate with the RB gene product; the possible involvement of this protein in E1A-mediated TNF cytotoxicity is discussed. Taken together, these results indicate that conserved regions 1 and 2 are required for E1A-mediated TNF cytotoxicity. In contrast, maximal IL-1-augmented TNF cytotoxicity requires conserved region 3 as well as the nonconserved carboxyl-terminal region of the 13S E1A product.

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Green, Michelle L., and Teri E. Klein. "A Multidomain TIGR/Olfactomedin Protein Family with Conserved Structural Similarity in the N-terminal Region and Conserved Motifs in the C-terminal Region." Molecular & Cellular Proteomics 1, no. 5 (May 2002): 394–403. http://dx.doi.org/10.1074/mcp.m200023-mcp200.

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Piskurich, J. F., M. H. Blanchard, K. R. Youngman, J. A. France, and C. S. Kaetzel. "Molecular cloning of the mouse polymeric Ig receptor. Functional regions of the molecule are conserved among five mammalian species." Journal of Immunology 154, no. 4 (February 15, 1995): 1735–47. http://dx.doi.org/10.4049/jimmunol.154.4.1735.

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Abstract Transcytosis of polymeric Ig (pIg) by mucosal epithelial cells is mediated by the polymeric Ig receptor (pIgR). Here we describe the characterization of a 3095-bp mouse pIgR cDNA, which encodes a protein of 771 amino acids. Northern blot analysis detected a single mouse pIgR transcript of 3.9 kb, expressed at high levels in small intestine and liver, and at low levels in lung. Alignment of the amino acid sequences of mouse, rat, human, bovine, and rabbit pIgR revealed that functional regions of the molecule are conserved across species. In the extracellular region, conserved motifs include: a 23-amino acid pIg-binding site, 11 intradomain disulfide bonds, consensus sites for N-glycosylation, and a putative cleavage site at which the extracellular region of pIgR (secretory component) is released from the plasma membrane. A 10-amino acid sequence within the transmembrane region is highly conserved, possibly reflecting a mechanism for transmitting signals from the extracellular region to the cytoplasmic tail. Conservation within the cytoplasmic tail of pIgR is clustered in motifs that mediate polarized sorting, endocytosis, and transcytosis.

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McSweeney, Alice, Colin Davies, and Vernon Ward. "Cell Cycle Arrest is a Conserved Function of Norovirus VPg Proteins." Viruses 11, no. 3 (March 4, 2019): 217. http://dx.doi.org/10.3390/v11030217.

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Murine norovirus (MNV) viral protein genome-linked (VPg) manipulates the cell cycle to induce a G0/G1 arrest and gain a beneficial replication environment. All viruses of the norovirus genus encode a VPg protein; however, it is unknown if the G0/G1 arrest induced by MNV VPg is conserved in other members of the genus. RNA transcripts encoding a representative viral VPg from five norovirus genogroups were transfected into RAW-Blue murine macrophages, and the percentage of cells in each phase of the cell cycle was determined. A G0/G1 cell cycle arrest was observed for all norovirus VPg proteins tested, and in the wider Caliciviridae family the arrest was also conserved in rabbit hemorrhagic disease virus (RHDV) VPg and human sapovirus (HuSV) VPg. Truncation of MNV VPg shows that the first 62 amino acids are sufficient for a cell cycle arrest, and alignment of VPg sequences revealed a conserved motif in the N-terminal region of VPg. Analysis of VPg constructs with single N-terminal region point mutations, or exchange of N-terminal regions between VPg proteins, confirmed the importance of the N-terminal region for cell cycle arrest. These results provide evidence that G0/G1 cell cycle arrest is a conserved function of norovirus VPg proteins that involves the N-terminal region of these proteins.

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Mojo, Endrat. "Saminist�s Indigenous Knowledge In Water Conservation in North Karts Kendeng Sukolilo." KOMUNITAS: International Journal of Indonesian Society and Culture 7, no. 2 (June 3, 2015): 236–42. http://dx.doi.org/10.15294/komunitas.v7i2.4048.

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Saminist is indigenous peoples and a local communities at North karts Kendeng. Saminist expected that North Karts Kendeng maintained and conserved continuity to be able to contribute to the life around this region especially abundant water. Water is one of the main needs of living beings on Earth, besides that water is a primary requirement of farmers in farming communities. Saminist as traditional community who only permitted to be farmers still practice the environmental wisdom from their heritage which aims to preserve the natural environment so that they could alive depend on nature around, especially Saminist just sack their business of farming crops that are not market oriented as much farming is done farmers in general. They tried to maintain a relationship of harmony between communities around the North Karts Kendeng to conserve North Karts Kendeng region from mining destruction, the negative impacts from mining in this region was disappears of water and others impacts such as natural disaster, flood, rough, and danger of tornado. North Karts Kendeng Sukolilo have 79 springs and 24 caves spread across 3 sub-district namely Sukolilo, Kayen and Tambakromo. Abundant natural resources certainly is a gift that needs to be maintained and conserved. To maintain and conserve this region with planting the three, not mining the rocks, maintain local wisdom, and refusal cement industry in North Karts Kendeng Sukolilo.

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Shubin, Calla B., Rini Mayangsari, Ariel D. Swett, and Carol W. Greider. "Rif1 regulates telomere length through conserved HEAT repeats." Nucleic Acids Research 49, no. 7 (March 27, 2021): 3967–80. http://dx.doi.org/10.1093/nar/gkab206.

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Abstract In budding yeast, Rif1 negatively regulates telomere length, but the mechanism of this regulation has remained elusive. Previous work identified several functional domains of Rif1, but none of these has been shown to mediate telomere length. To define Rif1 domains responsible for telomere regulation, we localized truncations of Rif1 to a single specific telomere and measured telomere length of that telomere compared to bulk telomeres. We found that a domain in the N-terminus containing HEAT repeats, Rif1177–996, was sufficient for length regulation when tethered to the telomere. Charged residues in this region were previously proposed to mediate DNA binding. We found that mutation of these residues disrupted telomere length regulation even when Rif1 was tethered to the telomere. Mutation of other conserved residues in this region, which were not predicted to interact with DNA, also disrupted telomere length maintenance, while mutation of conserved residues distal to this region did not. Our data suggest that conserved amino acids in the region from 436 to 577 play a functional role in telomere length regulation, which is separate from their proposed DNA binding function. We propose that the Rif1 HEAT repeats region represents a protein-protein binding interface that mediates telomere length regulation.

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33

Ng, S. Y., P. Gunning, R. Eddy, P. Ponte, J. Leavitt, T. Shows, and L. Kedes. "Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes." Molecular and Cellular Biology 5, no. 10 (October 1985): 2720–32. http://dx.doi.org/10.1128/mcb.5.10.2720-2732.1985.

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We have assigned six members of the human beta-actin multigene family to specific human chromosomes. The functional gene, ACTB, is located on human chromosome 7, and the other assigned beta-actin-related sequences are dispersed over at least four different chromosomes including one locus assigned to the X chromosome. Using intervening sequence probes, we showed that the functional gene is single copy and that all of the other beta-actin related sequences are recently generated in evolution and are probably processed pseudogenes. The entire nucleotide sequence of the functional gene has been determined and is identical to cDNA clones in the coding and 5' untranslated regions. We have previously reported that the 3' untranslated region is well conserved between humans and rats (Ponte et al., Nucleic Acids Res. 12:1687-1696, 1984). Now we report that four additional noncoding regions are evolutionarily conserved, including segments of the 5' flanking region, 5' untranslated region, and, surprisingly, intervening sequences I and III. These conserved sequences, especially those found in the introns, suggest a role for internal sequences in the regulation of beta-actin gene expression.

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Ng, S. Y., P. Gunning, R. Eddy, P. Ponte, J. Leavitt, T. Shows, and L. Kedes. "Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes." Molecular and Cellular Biology 5, no. 10 (October 1985): 2720–32. http://dx.doi.org/10.1128/mcb.5.10.2720.

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We have assigned six members of the human beta-actin multigene family to specific human chromosomes. The functional gene, ACTB, is located on human chromosome 7, and the other assigned beta-actin-related sequences are dispersed over at least four different chromosomes including one locus assigned to the X chromosome. Using intervening sequence probes, we showed that the functional gene is single copy and that all of the other beta-actin related sequences are recently generated in evolution and are probably processed pseudogenes. The entire nucleotide sequence of the functional gene has been determined and is identical to cDNA clones in the coding and 5' untranslated regions. We have previously reported that the 3' untranslated region is well conserved between humans and rats (Ponte et al., Nucleic Acids Res. 12:1687-1696, 1984). Now we report that four additional noncoding regions are evolutionarily conserved, including segments of the 5' flanking region, 5' untranslated region, and, surprisingly, intervening sequences I and III. These conserved sequences, especially those found in the introns, suggest a role for internal sequences in the regulation of beta-actin gene expression.

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Wu, Jing. "Testing the Coding Potential of Conserved Short Genomic Sequences." Advances in Bioinformatics 2010 (March 8, 2010): 1–8. http://dx.doi.org/10.1155/2010/287070.

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Proposed is a procedure to test whether a genomic sequence contains coding DNA, called a coding potential region. The procedure tests the coding potential of conserved short genomic sequence, in which the assumptions on the probability models of gene structures are relaxed. Thus, it is expected to provide additional candidate regions that contain coding DNAs to the current genomic database. The procedure was applied to the set of highly conserved human-mouse sequences in the genome database at the University of California at Santa Cruz. For sequences containing RefSeq coding exons, the procedure detected 91.3% regions having coding potential in this set, which covers 83% of the human RefSeq coding exons, at a 2.6% false positive rate. The procedure detected 12,688 novel short regions with coding potential at the false discovery rate <0.05; 65.7% of the novel regions are between annotated genes.

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Gonzalez-Magaldi, Monica, Jacqueline M. McCabe, Haley N. Cartwright, Ningze Sun, and Daniel J. Leahy. "Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity." Biochemical Journal 477, no. 21 (November 9, 2020): 4207–20. http://dx.doi.org/10.1042/bcj20200702.

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Receptor Tyrosine Kinases (RTKs) comprise a diverse group of cell-surface receptors that mediate key signaling events during animal development and are frequently activated in cancer. We show here that deletion of the extracellular regions of 10 RTKs representing 7 RTK classes or their substitution with the dimeric immunoglobulin Fc region results in constitutive receptor phosphorylation but fails to result in phosphorylation of downstream signaling effectors Erk or Akt. Conversely, substitution of RTK extracellular regions with the extracellular region of the Epidermal Growth Factor Receptor (EGFR) results in increases in effector phosphorylation in response to EGF. These results indicate that the activation signal generated by the EGFR extracellular region is capable of activating at least seven different RTK classes. Failure of phosphorylated Fc-RTK chimeras or RTKs with deleted extracellular regions to stimulate phosphorylation of downstream effectors indicates that either dimerization and receptor phosphorylation per se are insufficient to activate signaling or constitutive dimerization leads to pathway inhibition.

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37

Vikkula, M., M. Metsäranta, A. C. Syvänen, L. Ala-Kokko, E. Vuorio, and L. Peltonen. "Structural analysis of the regulatory elements of the type-II procollagen gene. Conservation of promoter and first intron sequences between human and mouse." Biochemical Journal 285, no. 1 (July 1, 1992): 287–94. http://dx.doi.org/10.1042/bj2850287.

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Transcription of the type-II procollagen gene (COL2A1) is very specifically restricted to a limited number of tissues, particularly cartilages. In order to identify transcription-control motifs we have sequenced the promoter region and the first intron of the human and mouse COL2A1 genes. With the assumption that these motifs should be well conserved during evolution, we have searched for potential elements important for the tissue-specific transcription of the COL2A1 gene by aligning the two sequences with each other and with the available rat type-II procollagen sequence for the promoter. With this approach we could identify specific evolutionarily well-conserved motifs in the promoter area. On the other hand, several suggested regulatory elements in the promoter region did not show evolutionary conservation. In the middle of the first intron we found a cluster of well-conserved transcription-control elements and we conclude that these conserved motifs most probably possess a significant function in the control of the tissue-specific transcription of the COL2A1 gene. We also describe locations of additional, highly conserved nucleotide stretches, which are good candidate regions in the search for binding sites of yet-uncharacterized cartilage-specific transcription regulators of the COL2A1 gene.

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38

Lin, Quan, Yasuko Rikihisa, Norio Ohashi, and Ning Zhi. "Mechanisms of Variable p44 Expression by Anaplasma phagocytophilum." Infection and Immunity 71, no. 10 (October 2003): 5650–61. http://dx.doi.org/10.1128/iai.71.10.5650-5661.2003.

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ABSTRACT The human intragranulocytic bacterium Anaplasma phagocytophilum promotes variation of P44s, which are surface-exposed proteins encoded by a p44 multigene family. In the present study, the specific p44 gene expression loci in four strains of A. phagocytophilum were identified and it was determined that each consisted of four tandem genes, tr1, omp-1X, omp-1N, and p44. A putative σ70-type promoter was found upstream of tr1. The p44 genes include a central hypervariable region flanked by conserved regions. The hypervariable region sequence in the p44 expression locus was duplicated and, regardless of the expression status, conserved at another locus in both low- and high-passage cell cultures of strain NY-37. No significant differences in the hypervariable region were found when we compared p44 sequences, at the level of cDNA, within the expression locus and within other loci in the genomes of strains NY-37 and HZ. Similarly, in cDNA isolated from patients and from assorted cultures of strains NY-31, NY-36, and NY-37, hypervariable regions of 450 deduced amino acid sequences of various p44s within each strain were found to be identical, as were those of p44 sequences in the genome of strain HZ. These data suggest that variations in p44 sequences at the level of the p44 expression locus occur through unidirectional conversion of the entire (nonsegmental) p44 hypervariable region including flanking regions with a corresponding sequence copied from one of the conserved donor p44 genomic loci. The data suggest that the P44 antigenic repertoire within the hypervariable region is restricted.

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39

Yurina, Valentina. "Coronavirus epitope prediction from highly conserved region of spike protein." Clinical and Experimental Vaccine Research 9, no. 2 (2020): 169. http://dx.doi.org/10.7774/cevr.2020.9.2.169.

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Niesters, H. G., and J. H. Strauss. "Mutagenesis of the conserved 51-nucleotide region of Sindbis virus." Journal of Virology 64, no. 4 (1990): 1639–47. http://dx.doi.org/10.1128/jvi.64.4.1639-1647.1990.

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Matsumiya, Y., K. Nishikawa, K. Inouye, and M. Kubo. "Mutational effect for stability in a conserved region of thermolysin." Letters in Applied Microbiology 40, no. 5 (May 2005): 329–34. http://dx.doi.org/10.1111/j.1472-765x.2005.01677.x.

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Miserez, A. R., H. Scharnagl, P. Y. Muller, R. Mirsaidi, H. B. Stähelin, A. Monsch, W. März, and M. M. Hoffmann. "Apolipoprotein E3Basel : new insights into a highly conserved protein region." European Journal of Clinical Investigation 33, no. 8 (July 16, 2003): 677–85. http://dx.doi.org/10.1046/j.1365-2362.2003.01180.x.

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43

Guan, Guijun, Meisheng Yi, Tohru Kobayashi, Yunhan Hong, and Yoshitaka Nagahama. "A Syntenic Region Conserved from Fish to Mammalian X Chromosome." International Journal of Evolutionary Biology 2014 (November 18, 2014): 1–10. http://dx.doi.org/10.1155/2014/873935.

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Sex chromosomes bearing the sex-determining gene initiate development along the male or female pathway, no matter which sex is determined by XY male or ZW female heterogamety. Sex chromosomes originate from ancient autosomes but evolved rapidly after the acquisition of sex-determining factors which are highly divergent between species. In the heterogametic male system (XY system), the X chromosome is relatively evolutionary silent and maintains most of its ancestral genes, in contrast to its Y counterpart that has evolved rapidly and degenerated. Sex in a teleost fish, the Nile tilapia (Oreochromis niloticus), is determined genetically via an XY system, in which an unpaired region is present in the largest chromosome pair. We defined the differences in DNA contents present in this chromosome with a two-color comparative genomic hybridization (CGH) and the random amplified polymorphic DNA (RAPD) approach in XY males. We further identified a syntenic segment within this region that is well conserved in several teleosts. Through comparative genome analysis, this syntenic segment was also shown to be present in mammalian X chromosomes, suggesting a common ancestral origin of vertebrate sex chromosomes.

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Nath Neerukonda, Sabari, Russell Vassell, and Carol D. Weiss. "Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin." Vaccines 8, no. 3 (July 12, 2020): 382. http://dx.doi.org/10.3390/vaccines8030382.

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Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.

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Karoussiotis, Christos, Maria Marti‐Solano, Tomasz Maciej Stepniewski, Alexandra Symeonof, Jana Selent, and Zafiroula Georgoussi. "A highly conserved δ‐opioid receptor region determines RGS4 interaction." FEBS Journal 287, no. 4 (September 9, 2019): 736–48. http://dx.doi.org/10.1111/febs.15033.

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Lamoyi, Edmundo, Anne L. Angiolillo, and Rose G. Mage. "An evolutionarily conserved rabbit T-cell receptor ?-chain variable region." Immunogenetics 23, no. 4 (April 1986): 266–70. http://dx.doi.org/10.1007/bf00373022.

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Zhang, Xianglilan, Huaixing Kang, Yuyuan Li, Xiaodong Liu, Yu Yang, Shasha Li, Guangqian Pei, et al. "Conserved termini and adjacent variable region of Twortlikevirus Staphylococcus phages." Virologica Sinica 30, no. 6 (December 2015): 433–40. http://dx.doi.org/10.1007/s12250-015-3643-y.

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48

Yoshii, Kentaro, Manabu Igarashi, Osamu Ichii, Kana Yokozawa, Kimihito Ito, Hiroaki Kariwa, and Ikuo Takashima. "A conserved region in the prM protein is a critical determinant in the assembly of flavivirus particles." Journal of General Virology 93, no. 1 (January 1, 2012): 27–38. http://dx.doi.org/10.1099/vir.0.035964-0.

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Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. In this study, a highly conserved region in the prM protein was identified among flaviviruses. In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the conserved region in the prM protein. Viral proteins were sparse in the Golgi complex and accumulated in the ER. Ultrastructural analysis revealed that long filamentous structures, rather than spherical SPs, were observed in the lumen of the ER as a result of the mutation. The production of infectious virions derived from infectious cDNA of TBEV was also reduced by mutations in the conserved region. Molecular modelling analysis suggested that the conserved region is important for the association of prM–envelope protein heterodimers in the formation of a spike of immature virion. These results are the first demonstration that the conserved region in the prM protein is a molecular determinant for the flavivirus assembly process.

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Cento, Valeria, Carmen Mirabelli, Salvatore Dimonte, Romina Salpini, Yue Han, Pascale Trimoulet, Ada Bertoli, et al. "Overlapping structure of hepatitis B virus (HBV) genome and immune selection pressure are critical forces modulating HBV evolution." Journal of General Virology 94, no. 1 (January 1, 2013): 143–49. http://dx.doi.org/10.1099/vir.0.046524-0.

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How the overlap between the hepatitis B virus (HBV) reverse transcriptase (RT) and HBV S antigen (HBsAg) genes modulates the extent of HBV genetic variability is still an open question, and was investigated here. The rate of nucleotide conservation (≤1 % variability) followed an atypical pattern in the RT gene, due to an overlap between RT and HBsAg (69.9 % nucleotide conservation in the overlapping region vs 41.2 % in the non-overlapping region; P<0.001), with a consequently lower rate of synonymous substitution within the overlapping region [median(interquartile range)dS = 3.1(1.5–7.4) vs 20.1(10.6–30.0); P = 3.249×10−22]. The most conserved RT regions were located within the YMDD motif and the N-terminal parts of the palm and finger domains, critical for RT functionality. These regions also corresponded to highly conserved HBsAg domains that are critical for HBsAg secretion. Conversely, the genomic region encoding the HBsAg antigenic loop (where immune-escape mutations are localized) showed a sharp decrease in the extent of conservation (40.6 %), which was less pronounced in the setting of human immunodeficiency virus (HIV)-driven immune suppression (48.8 % in HIV–HBV co-infection vs 21.5 % in mono-infected patients; P = 0.020). In conclusion, the overlapping reading frame and the immune system appear to have shaped the patterns of RT and HBsAg genetic variability. Highly conserved regions in RT and HBsAg may deserve further attention as novel therapeutic targets.

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Gao, William, Thomas A. Jones, and Elena Rivas. "Discovery of 17 conserved structural RNAs in fungi." Nucleic Acids Research 49, no. 11 (June 4, 2021): 6128–43. http://dx.doi.org/10.1093/nar/gkab355.

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Abstract Many non-coding RNAs with known functions are structurally conserved: their intramolecular secondary and tertiary interactions are maintained across evolutionary time. Consequently, the presence of conserved structure in multiple sequence alignments can be used to identify candidate functional non-coding RNAs. Here, we present a bioinformatics method that couples iterative homology search with covariation analysis to assess whether a genomic region has evidence of conserved RNA structure. We used this method to examine all unannotated regions of five well-studied fungal genomes (Saccharomyces cerevisiae, Candida albicans, Neurospora crassa, Aspergillus fumigatus, and Schizosaccharomyces pombe). We identified 17 novel structurally conserved non-coding RNA candidates, which include four H/ACA box small nucleolar RNAs, four intergenic RNAs and nine RNA structures located within the introns and untranslated regions (UTRs) of mRNAs. For the two structures in the 3′ UTRs of the metabolic genes GLY1 and MET13, we performed experiments that provide evidence against them being eukaryotic riboswitches.

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Journal articles on the topic 'Conserved region'

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