Academic literature on the topic 'Domain-motif interaction'
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Journal articles on the topic "Domain-motif interaction"
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Pang, Erli, and Kui Lin. "Yeast protein–protein interaction binding sites: prediction from the motif–motif, motif–domain and domain–domain levels." Molecular BioSystems 6, no. 11 (2010): 2164. http://dx.doi.org/10.1039/c0mb00038h.
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Millard, Peter S., Konrad Weber, Birthe B. Kragelund, and Meike Burow. "Specificity of MYB interactions relies on motifs in ordered and disordered contexts." Nucleic Acids Research 47, no. 18 (August 10, 2019): 9592–608. http://dx.doi.org/10.1093/nar/gkz691.
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Abstract Physical interactions between members of the MYB and bHLH transcription factor (TF) families regulate many important biological processes in plants. Not all reported MYB–bHLH interactions can be explained by the known binding sites in the R3 repeat of the MYB DNA-binding domain. Noteworthy, most of the sequence diversity of MYB TFs lies in their non-MYB regions, which contain orphan small subgroup-defining motifs not yet linked to molecular functions. Here, we identified the motif mediating interaction between MYB TFs from subgroup 12 and their bHLH partners. Unlike other known MYB–bHLH interactions, the motif locates to the centre of the predicted disordered non-MYB region. We characterised the core motif, which enabled accurate prediction of previously unknown bHLH-interacting MYB TFs in Arabidopsis thaliana, and we confirmed its functional importance in planta. Our results indicate a correlation between the MYB–bHLH interaction affinity and the phenotypic output controlled by the TF complex. The identification of an interaction motif outside R3 indicates that MYB–bHLH interactions must have arisen multiple times, independently and suggests many more motifs of functional relevance to be harvested from subgroup-specific studies.
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Lim, Jia Jia, Youngjin Lee, Tue Tu Ly, Jung Youn Kang, Jung-Gyu Lee, Jun Yop An, Hyung-Seop Youn, et al. "Structural insights into the interaction of p97 N-terminus domain and VBM in rhomboid protease, RHBDL4." Biochemical Journal 473, no. 18 (September 12, 2016): 2863–80. http://dx.doi.org/10.1042/bcj20160237.
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RHBDL4 is an active rhomboid that specifically recognizes and cleaves atypical, positively charged transmembrane endoplasmic reticulum-associated degradation (ERAD) substrates. Interaction of valosin-containing protein (p97/VCP) and RHBDL4 is crucial to retrotranslocate polyubiquitinated substrates for ERAD pathway. Here, we report the first complex structure of VCP-binding motif (VBM) with p97 N-terminal domain (p97N) at 1.88 Å resolution. Consistent with p97 adaptor proteins including p47-ubiquitin regulatory X (UBX), gp78-VCP-interacting motif (VIM), OTU1-UBX-like element, and FAF1-UBX, RHBDL4 VBM also binds at the interface between the two lobes of p97N. Notably, the RF residues in VBM are involved in the interaction with p97N, showing a similar interaction pattern with that of FPR signature motif in the UBX domain, although the directionality is opposite. Comparison of VBM interaction with VIM of gp78, another α-helical motif that interacts with p97N, revealed that the helix direction is inversed. Nevertheless, the conserved arginine residues in both motifs participate in the majority of the interface via extensive hydrogen bonds and ionic interactions with p97N. We identified novel VBM-binding mode to p97N that involves a combination of two types of p97–cofactor specificities observed in the UBX and VIM interactions. This highlights the induced fit model of p97N interdomain cleft upon cofactor binding to form stable p97–cofactor complexes. Our mutational and biochemical analyses in defining the specific interaction between VBM and p97N have elucidated the importance of the highly conserved VBM, applicable to other VBM-containing proteins. We also showed that RHBDL4, ubiquitins, and p97 co-operate for efficient substrate dislocation.
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Nielsen, Anders Lade, Poul Jørgensen, Thierry Lerouge, Margarita Cerviño, Pierre Chambon, and Régine Losson. "Nizp1, a Novel Multitype Zinc Finger Protein That Interacts with the NSD1 Histone Lysine Methyltransferase through a Unique C2HR Motif." Molecular and Cellular Biology 24, no. 12 (June 15, 2004): 5184–96. http://dx.doi.org/10.1128/mcb.24.12.5184-5196.2004.
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ABSTRACT Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and rearrangements of this gene by translocation can cause acute myeloid leukemia. The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors. We describe here a novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain, and four consensus C2H2-type zinc fingers preceded by a unique finger derivative, referred to herein as the C2HR motif. The C2HR motif functions to mediate protein-protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)-dependent fashion, and when tethered to RNA polymerase II promoters, represses transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription. Interestingly, converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect. Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif.
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Bardwell, V. J., and R. Treisman. "The POZ domain: a conserved protein-protein interaction motif." Genes & Development 8, no. 14 (July 15, 1994): 1664–77. http://dx.doi.org/10.1101/gad.8.14.1664.
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He, Bin, and Elizabeth M. Wilson. "Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs." Molecular and Cellular Biology 23, no. 6 (March 15, 2003): 2135–50. http://dx.doi.org/10.1128/mcb.23.6.2135-2150.2003.
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ABSTRACT Coactivator recruitment by activation function 2 (AF2) in the steroid receptor ligand binding domain takes place through binding of an LXXLL amphipathic α-helical motif at the AF2 hydrophobic surface. The androgen receptor (AR) and certain AR coregulators are distinguished by an FXXLF motif that interacts selectively with the AR AF2 site. Here we show that LXXLL and FXXLF motif interactions with steroid receptors are modulated by oppositely charged residues flanking the motifs and charge clusters bordering AF2 in the ligand binding domain. An increased number of charged residues flanking AF2 in the ligand binding domain complement the two previously characterized charge clamp residues in coactivator recruitment. The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model.
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Pascoe, Heath G., Stephen Gutowski, Hua Chen, Chad A. Brautigam, Zhe Chen, Paul C. Sternweis, and Xuewu Zhang. "Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ–RhoGEF." Proceedings of the National Academy of Sciences 112, no. 48 (November 16, 2015): 14852–57. http://dx.doi.org/10.1073/pnas.1508931112.
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PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligands in the cell. Plexins are transmembrane receptors that regulate processes such as axon guidance and angiogenesis. Two related guanine nucleotide exchange factors (GEFs), PDZ–RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling. Here, we present the crystal structure of the full-length cytoplasmic region of PlexinB2 in complex with the PDZ domain of PDZ–RhoGEF. The structure reveals that, in addition to the canonical C-terminal motif/PDZ interaction, the 3D domain of PlexinB2 forms a secondary interface with the PDZ domain. Our biophysical and cell-based assays show that the secondary interface contributes to the specific interaction between plexin and PDZ–RhoGEF and to signaling by plexin in the cell. Formation of secondary interfaces may be a general mechanism for increasing affinity and specificity of modular domain-mediated interactions.
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Litvinov, Rustem I., Marco Mravic, Hua Zhu, John W. Weisel, William F. DeGrado, and Joel S. Bennett. "Unique transmembrane domain interactions differentially modulate integrin αvβ3 and αIIbβ3 function." Proceedings of the National Academy of Sciences 116, no. 25 (June 3, 2019): 12295–300. http://dx.doi.org/10.1073/pnas.1904867116.
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Lateral transmembrane (TM) helix–helix interactions between single-span membrane proteins play an important role in the assembly and signaling of many cell-surface receptors. Often, these helices contain two highly conserved yet distinct interaction motifs, arranged such that the motifs cannot be engaged simultaneously. However, there is sparse experimental evidence that dual-engagement mechanisms play a role in biological signaling. Here, we investigate the function of the two conserved interaction motifs in the TM domain of the integrin β3-subunit. The first motif uses reciprocating “large-large-small” amino acid packing to mediate the interaction of the β3 and αIIb TM domains and maintain the inactive resting conformation of the platelet integrin αIIbβ3. The second motif, S-x3-A-x3-I, is a variant of the classical “G-x3-G” motif. Using site-directed mutagenesis, optical trap-based force spectroscopy, and molecular modeling, we show that S-x3-A-x3-I does not engage αIIb but rather mediates the interaction of the β3 TM domain with the TM domain of the αv-subunit of the integrin αvβ3. Like αIIbβ3, αvβ3 on circulating platelets is inactive, and in the absence of platelet stimulation is unable to interact with components of the subendothelial matrix. However, disrupting any residue in the β3 S-x3-A-x3-I motif by site-directed mutations is sufficient to induce αvβ3 binding to the αvβ3 ligand osteopontin and to the monoclonal antibody WOW-1. Thus, the β3-integrin TM domain is able to engage in two mutually exclusive interactions that produce alternate α-subunit pairing, creating two integrins with distinct biological functions.
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Brady, Troy L., Peter G. Fuerst, Robert A. Dick, Clarice Schmidt, and Daniel F. Voytas. "Retrotransposon Target Site Selection by Imitation of a Cellular Protein." Molecular and Cellular Biology 28, no. 4 (December 17, 2007): 1230–39. http://dx.doi.org/10.1128/mcb.01502-07.
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ABSTRACT Mobile elements rely on cellular processes to replicate, and therefore, mobile element proteins frequently interact with a variety of cellular factors. The integrase (IN) encoded by the retrotransposon Ty5 interacts with the heterochromatin protein Sir4, and this interaction determines Ty5's preference to integrate into heterochromatin. We explored the hypothesis that Ty5's targeting mechanism arose by mimicking an interaction between Sir4 and another cellular protein(s). Mutational analyses defined the requirements for the IN-Sir4 interaction, providing criteria to screen for cellular analogues. Esc1, a protein associated with the inner nuclear membrane, interacted with the same domain of Sir4 as IN, and 75% of mutations that disrupted IN-Sir4 interactions also abrogated Esc1-Sir4 interactions. A small motif critical for recognizing Sir4 was identified in Esc1. The functional equivalency of this motif and the Sir4-interacting domain of IN was demonstrated by swapping these motifs and showing that the chimeric IN and Esc1 proteins effectively target integration and partition DNA, respectively. We conclude that Ty5 targets integration by imitating the Esc1-Sir4 interaction and suggest molecular mimicry as a general mechanism that enables mobile elements to interface with cellular processes.
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Gurung, Raju, Darlami Om, Rabin Pun, Soonsil Hyun, and Dongyun Shin. "Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders." Cancers 15, no. 15 (August 1, 2023): 3910. http://dx.doi.org/10.3390/cancers15153910.
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WD40-repeat (WDR) domain proteins play a crucial role in mediating protein–protein interactions that sustain oncogenesis in human cancers. One prominent example is the interaction between the transcription factor MYC and its chromatin co-factor, WD40-repeat domain protein 5 (WDR5), which is essential for oncogenic processes. The MYC family of proteins is frequently overexpressed in various cancers and has been validated as a promising target for anticancer therapies. The recruitment of MYC to chromatin is facilitated by WDR5, highlighting the significance of their interaction. Consequently, inhibiting the MYC–WDR5 interaction has been shown to induce the regression of malignant tumors, offering an alternative approach to targeting MYC in the development of anticancer drugs. WDR5 has two protein interaction sites, the “WDR5-binding motif” (WBM) site for MYC interaction and the histone methyltransferases SET1 recognition motif “WDR5-interacting” (WIN) site forming MLL complex. Significant efforts have been dedicated to the discovery of inhibitors that target the WDR5 protein. More recently, the successful application of targeted protein degradation technology has enabled the removal of WDR5. This breakthrough has opened up new avenues for inhibiting the interaction between WDR5 and the binding partners. In this review, we address the recent progress made in targeting WDR5 to inhibit MDR5–MYC and MDR5–MLL1 interactions, including its targeted protein degradation and their potential impact on anticancer drug discovery.
Dissertations / Theses on the topic "Domain-motif interaction"
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Vivona, Sandro. "VAMP7: a model system to study the Longin Domain-SNARE motif." Doctoral thesis, Università degli studi di Padova, 2009. http://hdl.handle.net/11577/3421900.
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Eukaryotic cells rely on a complex system of membrane-enclosed compartments that are maintained by the trafficking of shuttling vesicles. The fusion of these vesicles with the target compartment relies on multiprotein complexes that have been conserved throughout eukaryotic evolution. SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins are considered the engine of membrane fusion in all trafficking pathways of the cell. Upon specific protein-protein interactions, SNARE proteins that are localized in opposing membranes form a four helix bundle that releases free energy and induces membrane fusion. The SNARE motif is the elementary unit of this bundle and defines all SNARE proteins.
SNARE proteins possess other regulatory domains that contribute in modulating the specificity of the fusion event. One of these accessory elements is the Longin Domain (LD). Other than being well conserved among all eukaryotes, the LD is not limited to SNAREs only and is present in many molecular processes related to the life cycle of vesicles. LD-containing SNAREs are called Longins and are divided in three main subfamilies: Ykt6p, Sec22b, VAMP7. The Longin Domain (LD) is usually composed of about 120 amino acids arranged in a globular structural fold that consists of five ? strands (?1- ?5) sandwiched by one ? helix (?1) on one side and two helices (?2 and ?3) on the other side.
The LD can fold back onto the SNARE motif in Ykt6p and Sec22b but not in Nyv1p – a fourth minor longin subfamily. This intramolecular interaction involves a surface-exposed hydrophobic pocket contributed by the ?1-?3 structural elements, which is bound by the SNARE motif. This mechanism eventually inhibits and prevents unspecific formation of the SNARE complex, thus regulating the vesicle fusion process.
However, very little is known about the dynamic properties of such mechanism. The present study uses VAMP7 as a model system to reveal these characteristics. Our interest in VAMP7 relies on the fact that not only VAMP7 lacks any direct evidence of the LD-SNARE interaction, but it also offers a system of natural variations to the usual LD-SNARE domain arrangement that can prove extremely useful in our study. The present work reveals unknown dynamic properties of the LD-SNARE interaction supporting a dominantly “closed conformation” for Longins, with heterogeneous characteristics. The results shown in this research complement well with what we already know about a similar auto-inhibitory mechanism observed in the Syntaxin subfamily of SNAREs. Therefore, we provide here new bases for a better understanding of the regulatory mechanisms involved in vesicle fusion.Le cellule eucariote sono caratterizzate da un complesso sistema di membrane, che offre svariate compartimentazioni con diverse condizioni chimico-fisiche. Se da una parte tale sistema permette la realizzazione di un’ampia gamma di processi biochimici, dall’altra richiede un altrettanto complesso sistema di interscambio atto al suo mantenimento. Tale interscambio è assicurato dal trafficking di vescicole che originano da un compartimento donatore e riversano il loro contenuto in un compartimento accettore attraverso un processo che richiede la fusione delle membrane lipidiche. Tale processo si fonda sull’organizzazione di complessi macromolecolari a cui contribuiscono varie famiglie proteiche ben conservate attraverso l’evoluzione eucariotica. La famiglia delle SNARE è una di queste. Le SNAREs sono considerate i motori della fusione di membrane. La loro capacità di formare complessi specifici in trans tra le due memrane su cui risiedono fornisce il contributo energetico necessario a indurre la fusione degli strati lipidici. Tali complessi consistono in un intreccio di quattro eliche chiamate SNARE motifs, domini di circa 60-70 amino acidi che definiscono tutte le SNAREs. Oltre allo SNARE motif, le SNAREs contengono spesso domini accessori a funzione regolativa. Uno di questi è il Longin Domain (LD). Il LD non è limitato alle sole SNAREs e anzi si ritrova in altre famiglie proteiche tutte coinvolte in processi molecolari riguardanti il ciclo vitale di una vescicola. Nelle SNAREs, il LD definisce una famiglia chiamata Longins, suddivisa a sua volta nelle proteine Ykt6, Sec22b e VAMP7. Il LD consiste di circa 120 aminoacidi organizzati in una struttura spaziale globulare che comprende un piano di cinque foglietti ? (?1- ?5), complessati da un’alfa elica (?1) su un lato e da altre due eliche (?2-?3) sull’altro. In Ykt6 e Sec22b si è dimostrata la possibilità che il LD si ripieghi sullo SNARE motif e lo coordini su una sua superficie idrofobica compresa tra ?1 e ?3. Questo meccanismo si è dimostrato in grado di prevenire la formazione di complessi SNARE non specifici. Tuttavia ben poco si conosce ad oggi sulla natura di questa interazione in termini dinamici, a differenza di quanto invece si sa per un analogo meccanismo osservato nella famiglia SNARE delle Sintaxine. In altri temrini non è dato sapere se nelle Longine questo meccanismo implica una conformazione stabilmente “chiusa” di LD e SNARE, o se piuttosto esso si realizza come un equilibrio dinamico tra conformazioni aperte e chiuse. Una serie di motivi, tra cui l’assenza di dati diretti per questo fenomeno in VAMP7 e la possibilità di usufruire di sue varianti naturali, ci hanno spinto a scegliere VAMP7 come sistema modello per fornire le risposte ai suddetti interrogativi. I nostri dati suggeriscono per le Longine una conformazione stabilmente chiusa, ma non omogenea e capace di cambi conformazionali molto rapidi. Questo lavoro complementa bene quanto già noto per le sintaxine e fornisce dunque la possibilità di comprendere meglio i meccanismi regolativi gneralmente adottati nella fusione vescicolare.
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COSTA, STEFANO. "PepspotDB: una banca dati per l'immagazzinamento e l'analisi di esperimenti basati sulla tecnologia degli array di peptidi." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/984.
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La mappatura dell'interattoma (la rete composta da tutte le possibili interazioni fisiche proteina-proteina che avvengono naturalmente in una cellula o in un organismo) degli organismi viventi è una risorsa essenziale per promuovere l'avanzamento della Systems Biology. Senza sminuire le tante preziose lezioni che abbiamo appreso dallo studio delle reti di interazioni proteina-proteina, occorre però onestamente riconoscere che gli interattomi attuali presentano diverse limitazioni, tra cui cruciale è la scarsità di informazione sulle regioni proteiche coinvolte nel legame. A questo proposito, risultano particolarmente importanti alcune famiglie di domini proteici (ad es. SH2, SH3, WW, EVH1), capaci di mediare interazioni proteina-proteina legandosi a brevi motivi lineari.
Recentemente, il nostro gruppo ha sviluppato una strategia basata sulla tecnologia degli array di peptidi per studiare, su larga scala, la specificità di riconoscimento dei domini che legano brevi sequenze peptidiche. Il nostro approccio consta di una parte sperimentale ed una computazionale: 1) il profilo di riconoscimento di ciascun dominio viene determinato saggiando l'interazione fra il dominio e un array di peptidi appositamente progettato; 2) una rete neurale viene “addestrata” su ciascuno dei profili ottenuti e le predizioni vengono integrate, mediante un approccio statistico di tipo Naїve Bayes, con informazioni eterogenee e indipendenti fra loro, al fine di ottenere un punteggio globale di affidabilità dell'interazione. Questo approccio è stato impiegato per identificare tutte le interazioni tra coppie di proteine umane mediate da domini SH2.
A supporto dei progetti che adottano l'approccio descritto, abbiamo sviluppato una nuova applicazione basata su banca dati, chiamata PepspotDB, pensata specificamente per facilitare l'immagazzinamento e l'analisi di saggi di interazione molecolare che fanno uso della tecnologia degli array di peptidi. Nutriamo la speranza che PepspotDB possa maturare al punto da diventare una risorsa di spicco per il recupero e l'analisi di dati provenienti da esperimenti con array di peptidi.
PepspotDB è composto da una classica banca dati relazionale, dove vengono immagazzinati risultati sperimentali, predizioni computazionali e dati estratti dalla letteratura o altre fonti d'informazione esterne, una applicazione web, che fornisce una interfaccia semplice, ma potente, alla banca dati e un insieme di strumenti per il trattamento semi-automatico dei dati sperimentali “grezzi”, l'identificazione di buoni candidati partner di legame e la visualizzazione di logo di sequenze.
Al momento della stesura di questa tesi, PepspotDB contiene più di 5 milioni di record, che comprendono circa 80 esperimenti e 55.548 interazioni dominio-peptide fra 70 domini SH2 e 7.972 peptidi distinti. Questi numeri si raddoppieranno presto e continueranno a crescere man mano che vengono completati nuovi esperimenti su domini appartenenti ad altre famiglie.
Ci auguriamo che gli scienziati interessati allo studio delle interazioni proteina-proteina mediate da domini che riconoscono brevi peptidi lineari possano trovare in PepspotDB un valido alleato per promuovere la propria ricerca.The mapping of the “interactome” (i.e. the network comprising all possible physical protein-protein interactions naturally occurring within a cell or an organism) of living organisms is a key asset to promote the advancement of Systems Biology. Notwithstanding the numerous insights we have gained from the study of protein-protein interaction networks, currently available interactomes present several shortcomings, one of the more crucial being the lack of information regarding the regions involved in the interactions. Especially important in this respect are several families of conserved protein domains (e. g. SH2, SH3, WW, EVH1) that mediate protein-protein interactions by binding to short linear motifs. Our group has recently devised a strategy based on peptide array technology to study on a large scale the target recognition specificity of domains binding to short peptides. Our approach consists of an experimental and a computational part: 1) the domains are profiled by testing them with ad hoc designed peptide arrays; 2) Neural Network based predictors are trained for each of the profiled domains and the predictions are combined in a Bayesian framework with information coming from multiple orthogonal sources to obtain an integrated interaction confidence score. The approach has been applied to the identification of all human protein-protein interactions mediated by SH2 domains. To support the projects employing our approach, we have developed a brand new database-centered application, called PepspotDB, specifically designed to facilitate the storage and analysis of molecular interaction assays exploiting peptide array technology. We hope that PepspotDB will grow enough to become a prominent resource for the storage, analysis and retrieval of peptide chip data. PepspotDB comes with a traditional relational database, where experimental results, computational predictions and data imported from the literature or other external sources are stored, a rich web application, providing a user-friendly, yet powerful, interface to the database, and a set of tools to automatically process raw experimental data, identify promising candidate binders and visualize sequence logos. At the time of writing, PepspotDB contains more than 5 million records, comprising about 80 experiments and 55,548 domain-peptide interactions involving 70 SH2 domains and 7,972 unique peptides. These numbers are bound to more than double as new experiments involving other domain families are completed. Scientists studying protein-protein interactions mediated by domains recognizing linear peptides may find PepspotDB a precious resource to foster their own research.
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Berardi, A. "STRUCTURAL INSIGHTS INTO THE INTERACTION BETWEEN THE TANDEM PHD FINGER DOMAIN P5C5 OF NSD1 AND THE ZINC FINGER MOTIF C2HR OF NIZP1." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/247139.
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Point Mutations or translocation in NSD1 cause the overgrowth disorder Sotos syndrome and acute myeloid leukemia (AML), respectively (Berdasco M. et al, 2009, Wang G et al, 2003). NSD1 contains several chromatin related domains including a SET domain responsible for histone methyltranferases activity (H3K36 and H4K20), two nuclear receptor-interaction (NID) motifs, five zinc finger domains (PHD1-5), a variant PHD finger (C5HCH), two proline-tryptophan-proline-tryptophan (PWWP1-2) domains (Lucio-Eterovic AK, et al , 2011), suggesting a role in chromatin regulation and gene expression. 20 pathological Sotos mutations have been detected on the PHD tandem domain composed by NSD1-PHD5 and NSD1-C5HCH (NSD1-P5C5). The tandem domain is essential for the pathogenesis of acute myeloid leukaemia (AML) caused by the chimeric protein NUP98/NSD1 that forces the abnormal activation of Hox-A and Meis1 genes (Wang at al 2007). The deletion of this tandem domain is sufficient to abolish NUP98/NSD1 interaction with chromatin, preventing both the transcription activation of HOX genes and the immortalization of myeloid progenitors. The biological role of NSD1-P5C5 is still unclear. It was proposed that this tandem domain is involved in the recognition of both H3K4me3 and H3K9me3 histone marks, (Pasillas M et al. 2011). However, biophysical experiments in our laboratory did not confirm these results challenging the idea that this tandem domain can really work as epigenetic reader. Previous biochemical studies suggested that NSD1-P5C5 can also work as protein-protein interaction motif, being able to bind to the co-repressor Nizp1 by its C2HR zinc fingers motif (Nizp1-C2HR) thus mediating gene repression (Nielsen AL et al, 2004).
The structural determinants of this interaction are still unknown and have been object of this thesis. In order to get more insights into the physiological and pathological role of NSD1-P5C5, we have solved its (i) solution structure by NMR spectroscopy and (ii) characterized its interaction with Nizp1-C2HR.
NSD1-P5C5 folds as unique functional unit adopting a “face to side orientation”. In particular NSD1-PHD5 (or NSD1-P5) presents the canonical PHD finger fold, whereas the NSD1-C5HCH (or NSD1-C5) domain displays an atypical topology characterized by the presence of an additional two stranded β-sheet. In order to investigate the impact of Sotos point mutation on NSD1-P5C5 we expressed and purified seven mutants and analyzed them by NMR. The majority of them destabilize the fold, with the exception of the solvent exposed mutation Arg2152Gln and His2205Arg suggesting a functional role for these residues.
We next solved the solution structure of the zinc finger Nizp1-C2HR, an atypical Cys2His2-type zinc finger in which the fourth zinc chelating residue is substituted by an arginine residue. Its fold consists of a short α-helix and of a short two-stranded β-sheet hold together by one zinc ion. Importantly, we showed that three zinc ligands are sufficient to maintain the protein domain fold and functionality.
NMR titrations of 15N labelled NSD1-P5C5 with Nizp1-C2HR and 15N labelled Nizp1-C2HR with NSD1-P5C5 clearly show that the two proteins directly interact. Analysis of the chemical shift displacements upon complex formation allowed to identify the residues of the two protein domains involved in protein-protein interaction. The interaction surface is located on the interface between NSD1-P5 and NSD1-C5 and on the α-helix of Nizp1-C2HR, respectively.
Based on this information using the software HADDOCK we have computed a data driven docking model of the protein complex. In the model Nizp1-C2HR places its α-helix in the groove at the interface between NSD1-P5 and NSD1-C5, creating both hydrophobic and polar intermolecular contacts.
The thermodynamic parameters that govern complex formation were studied by ITC titrations: the binding reaction is entropy-driven, with a stoichiometry of 1:1 and a Kd of 3,80±0,66 μM. In order to solve the structure of the protein complex we performed crystallographic screenings, and we have found preliminary conditions for obtaining single crystals.
In conclusion, the presented results provide novel information on the interaction between a tandem PHD finger domain and zinc finger motif. The results represent, to the best of our knowledge, the first biophysical characterization between two zinc binding domains. Most importantly, these data give the first molecular details of the interaction between NSD1 and Nizp1 and may provide useful insights into the function of NSD1 and its role in pathological conditions both in Sotos Syndrome and AML. Future work will be dedicated to the full three-dimensional characterization of the complex and to the analysis of Sotos mutations on complex formation.
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Reh, Juliane, Annett Stange, Anne Götz, Marlene Rönitz, Arend Große, and Dirk Lindemann. "An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127152.
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Background: Foamy viruses (FVs) have developed a unique budding strategy within the retrovirus family. FV release requires co-expression and a highly specific interaction between capsid (Gag) and glycoprotein (Env), which cannot be complemented by heterologous Env proteins. The interaction domain in FV Env has been mapped in greater detail and resides mainly in the N-terminal tip of the cytoplasmic domain of the Env leader peptide subunit. In contrast, the corresponding domain within Gag is less well defined. Previous investigations suggest that it is located within the N-terminal part of the protein.
Results: Here we characterized additional Gag interaction determinants of the prototype FV (PFV) isolate using a combination of particle release, GST pull-down and single cycle infectivity analysis assays. Our results demonstrate that a minimal PFV Gag protein comprising the N-terminal 129 aa was released into the supernatant, whereas proteins lacking this domain failed to do so. Fine mapping of domains within the N-terminus of PFV Gag revealed that the N-terminal 10 aa of PFV Gag were dispensable for viral replication. In contrast, larger deletions or structurally deleterious point mutations in C-terminally adjacent sequences predicted to harbor a helical region abolished particle egress and Gag – Env protein interaction. Pull-down assays, using proteins of mammalian and prokaryotic origin, support the previous hypothesis of a direct interaction of both PFV proteins without requirement for cellular cofactors and suggest a potential direct contact of Env through this N-terminal Gag domain. Furthermore, analysis of point mutants within this domain in context of PFV vector particles indicates additional particle release-independent functions for this structure in viral replication by directly affecting virion infectivity.
Conclusions: Thus, our results demonstrate not only a critical function of an N-terminal PFV Gag motif for the essential capsid - glycoprotein interaction required for virus budding but also point out additional functions that affect virion infectivity.
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Reh, Juliane, Annett Stange, Anne Götz, Marlene Rönitz, Arend Große, and Dirk Lindemann. "An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity." BioMed Central, 2013. https://tud.qucosa.de/id/qucosa%3A27282.
Full textAbstract:
Background: Foamy viruses (FVs) have developed a unique budding strategy within the retrovirus family. FV release requires co-expression and a highly specific interaction between capsid (Gag) and glycoprotein (Env), which cannot be complemented by heterologous Env proteins. The interaction domain in FV Env has been mapped in greater detail and resides mainly in the N-terminal tip of the cytoplasmic domain of the Env leader peptide subunit. In contrast, the corresponding domain within Gag is less well defined. Previous investigations suggest that it is located within the N-terminal part of the protein.
Results: Here we characterized additional Gag interaction determinants of the prototype FV (PFV) isolate using a combination of particle release, GST pull-down and single cycle infectivity analysis assays. Our results demonstrate that a minimal PFV Gag protein comprising the N-terminal 129 aa was released into the supernatant, whereas proteins lacking this domain failed to do so. Fine mapping of domains within the N-terminus of PFV Gag revealed that the N-terminal 10 aa of PFV Gag were dispensable for viral replication. In contrast, larger deletions or structurally deleterious point mutations in C-terminally adjacent sequences predicted to harbor a helical region abolished particle egress and Gag – Env protein interaction. Pull-down assays, using proteins of mammalian and prokaryotic origin, support the previous hypothesis of a direct interaction of both PFV proteins without requirement for cellular cofactors and suggest a potential direct contact of Env through this N-terminal Gag domain. Furthermore, analysis of point mutants within this domain in context of PFV vector particles indicates additional particle release-independent functions for this structure in viral replication by directly affecting virion infectivity.
Conclusions: Thus, our results demonstrate not only a critical function of an N-terminal PFV Gag motif for the essential capsid - glycoprotein interaction required for virus budding but also point out additional functions that affect virion infectivity.
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Jané, Palli Pau. "Quantification des affinités PBM/PDZ et de leurs sites modulateurs par des approches expérimentales et informatiques à haut débit." Electronic Thesis or Diss., Strasbourg, 2020. http://www.theses.fr/2020STRAJ051.
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Ce travail a porté sur les domaines PDZ, une famille de domaines globulaires reconnaissant des motifs de liaison aux PDZ (appelés PBM, pour ‘PDZ-Binding Motifs’) généralement situés à l'extrémité C-terminale de leurs protéines partenaires. Les réseaux domaines-motifs sont souvent modulés par des modifications post-traductionnelles réversibles (PTM). Nous avons utilisé des PBM synthétiques simulant différentes conditions: motifs sauvages de diverses longueurs, acétylés, phosphorylés ou portant des mutations ‘imitant’ les PTM. Ces peptides ont été utilisés pour des études d'interaction à l'aide du test ‘Hold-Up’, un test développé à l'origine dans notre laboratoire. Nous avons évalué l'impact de diverses modifications des complexes PBM/PDZ, qui conduisent à un changement global de leur capacité de liaison du PDZ. Ces résultats fournissent des informations quantitatives sur l'effet biologique que de telles modifications pourraient avoir dans le contexte des protéines entièresThis thesis focuses on PDZ domains, a family of globular domains that bind to conserved PDZ-Binding Motifs (called henceforth PBMs) generally situated at the extreme C-terminus of their partner proteins. Domain-motif networks are often modulated by reversible post-translational modifications (PTMs). We used synthetized PBMs to reproduce different conditions, such as a wild-type, acetylation or phosphorylation, addition of extra exosites or residue mimication of PTM in the literature. These peptides were used for interaction studies using the holdup assay, an assay originally developed in our laboratory. We evaluated the impact of diverse modifications of the PBM/PDZ interactions, which led to a global change of the PDZ-binding capability. These results provided quantitative information on the biological effects that such modifications may have in the context of full-length proteins
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Biasutto, Antonio. "Structural insights into human SNF2/SWI2 chromatin remodeler SMARCAD1 and its role in DNA repair." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:efc019ba-41ee-4dbd-adfb-2786017e91aa.
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ATP-dependent chromatin remodelers have been proposed to act sequentially, and to a certain extent non-redundantly, in the priming stages of the DNA Damage Response pathways by establishing chromatin in lesion sites ready to act as a scaffold for repair factors or to be displaced in order to allow DNA repair. Among remodeling factors proposed to play a role in DNA repair is SMARCAD1, a poorly characterized, non-canonical member of the SWR1-like family of SNF2/SWI2 superfamily of ATPases, which has recently been identified as a potential target for ATM/ATR phosphorylation at canonical and non-canonical sites upon DNA damage. The actual mechanism for SMARCAD1 recruitment and involvement in DNA remodeling is still unknown, and unlike most other chromatin remodelers, SMARCAD1 does not contain DNA- or histone-binding domains frequently accompanying such proteins. Instead, in addition to the core ATPase domain, only two CUE domains (a type of helical ubiquitin-binding domain) have been identified. This thesis presents the findings of an investigation intended to structurally characterize SMARCAD1 by dissecting and identifying its domain architecture, and examining the activity and ligand selectivity of its binding domains in the functional context of DNA damage repair. The solution NMR structure of the CUE1 domain is presented, describing a triple helix bundle consistent with other members of the family. Furthermore, a novel SUMO interacting motif was identified and through a combination of NMR titrations and phospho-proteomics analysis, shown to be constitutively phosphorylated which excludes the possibility of DNA damage dependent ATM targeting as the recruitment mechanism for DNA repair. Additionally, it is demonstrated that both CUE domains are poor binders of mono-ubiquitin, however CUE1 specifically mediates the high affinity binary interaction with the transcriptionally repressive master regulator KAP1. This interaction was shown to be independent of post-translational ubiquitylation but rather sustained through direct interaction with the dimeric RBCC domain of KAP1. Finally, mass spectrometry profiling of domain-dependent interactions (based on differential abundance relative to changes due to chemically induced DNA damage) suggests SMARCAD1 may be involved in p53 transcriptional regulation through interactions maintained with CUE1 prior to DNA damage, whereas the SIM domain selectively targets protein interactions upon DNA damage that simultaneously activate p53 transcriptional control and recruit SMARCAD1 to DNA damage repair pathways.
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Stein, Amelie. "Peptime-mediated interactions in high-resolution 3-dimensional structures." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7218.
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Proteins and protein interactions are involved in virtually all processes of life. Here we study interactions between globular domains and short linear motifs, which form a small interface ideal for transient interactions. Despite the small number of contacts involved, these domain-motif interactions (DMIs) are known to be highly specific in vivo. We have identified hundreds of instances of DMIs in high-resolution 3-dimensional (3D) structures to analyze the molecular basis of their high specificity. Furthermore, we have derived structural parameters to identify DMIs in 3D structures in a more general, motif-independent way. An important class of DMIs are kinase-substrate interactions. By combining the phosphorylation motif with different kinds of contextual information, we could predict substrates of the human kinase Aurora A. Lastly, we have incorporated DMIs into our database of 3D interacting domains (3did) to disseminate our results to the scientific community for future research. Los procesos moleculares subyacentes a la mayoría de funciones biológicas implican la participación directa de una infinidad de proteínas y múltiples interacciones entre ellas. En esta tesis estudiamos un tipo particular de estas interacciones, de carácter transitorio y altamente específicas, dónde un dominio globular en una proteína reconoce un corto péptido lineal en otra (DMIs). En concreto, identificamos múltiples casos de DMIs en estructuras tridimensionales (3D) de alta resolución y analizamos las bases moleculares de su especificidad. Además, derivamos parámetros estructurales globales que nos permiten identificar nuevos casos de DMIs. Así mismo, y como caso práctico, combinamos el motivo de fosforilación propio de la quinasa humana Aurora A con diversas clases de información contextual para predecir y validar 90 nuevos substratos. Por último, incorporamos las caracterizadas DMIs en nuestra base de datos de interacciones en 3D (3did) con el fin de diseminar nuestros resultados entre la comunidad científica.
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Liu, Shao-Hsuan, and 劉劭萱. "Characterization of the Interaction between Serine 269 Phosphorylated Aquaporin-2 PDZ Motif and Sipa1l1 Domain." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/13827132453844395362.
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碩士國立臺灣大學
生物化學暨分子生物學研究所
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Vasopressin regulates the amount of the water channel protein aquaporin-2 (AQP2) in the apical plasma membrane via enhancing exocytosis and/or reducing endocytosis of AQP2-containing vesicles to and from the apical plasma membrane of the kidney collecting duct cells. Previous studies suggest that vasopressin induces AQP2 phosphorylation at serine 269 (S269), which enhances retention of AQP2 in the apical plasma membrane. We previously identified Sipa1l1, a PDZ domain-containing protein that regulates apical retention of serine 269-phosphorylated AQP2. Sipa1l1 reduces its interaction with the serine 269 phosphorylated AQP2 PDZ motif. To directly measure this PDZ interaction, we expressed and purified the Sipa1l1 PDZ domain with fusion tags glutathione-S-transferase, thioredoxin, 6x His, and maltose binding protein. Surface plasmon resonance binding experiments showed weaker binding of the serine 269 phosphorylated AQP2 peptide to the Sipa1l1 PDZ compared with the serine 269 non-phosphorylated AQP2 peptide. Models of the Sipa1l1 PDZ domain-AQP2 PDZ motif complex showed phosphorylation at serine 269 of the AQP2 PDZ domain reduces its interaction with the Sipa1l1 PDZ domain.
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Cieplak-Rotowska, Maja. "Biophysical and molecular biology studies of proteins involved in gene silencing." Doctoral thesis, 2017. https://depotuw.ceon.pl/handle/item/2368.
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This thesis provides biophysical bases of the interactions between two proteins involved in microRNA (miRNA)-mediated silencing: CNOT1 and the silencing domain of GW182. The regulation of gene expression at the post-transcriptional level involves the crucial CCR4-NOT deadenylase complex, which deadenylates mRNA, and can also inhibit translation in an independent fashion. In miRNA-mediated silencing, the CCR4-NOT complex is brought into the vicinity of the target mRNA by the successive actions of the miRNA, the Argonaute protein and finally, the GW182 protein, which interacts directly with CCR4-NOT. In the case of silencing of mRNAs containing AU-rich elements, the same action is performed by the protein called tristetraprolin involved in the regulation of inflammatory processes. The interactions and interplay between all of these high molecular weight proteins are relatively poorly understood. In particular, the interaction sites between GW182 and the CCR4-NOT complex were previously unknown.
Molecular biology experiments allowed the identification of CCR4-NOT interaction motifs on GW182. One of them is crucial for deadenylation, while the other is vital in mediating the interaction with CCR4-NOT via CNOT1, the scaffolding subunit of the CCR4-NOT complex. Biophysical experiments based on hydrogen-deuterium exchange mass spectrometry allowed the identification of the corresponding binding site on CNOT1(800-999). Surprisingly, the binding site of the GW182 silencing domain was found to be at the same CNOT1(800-999) surface region as the binding site of tristetraprolin. Biochemical experiments excluded their simultaneous binding to CNOT1. The GW182 and tristetraprolin proteins share a common motif, RLPXφ, that interacts with CNOT1 in a very similar, but not identical, manner. This sequence has been proposed to act as a short linear motif. Thus, the two different gene silencing pathways: miRNA-mediated silencing and ARE-mediated silencing intersect at CNOT1, which serves as a molecular hub.
The structural dynamics of the GW182 silencing domain and the CNOT1(800-999) fragments were also studied. The GW182 silencing domain was experimentally proved to be natively unstructured except for an RNA-recognition motif (RRM) domain. The GW182 RRM domain was found to be a loose structure, contrary to the CNOT1(800-999) structure that was found to be very rigid.
Experiments performed in this thesis have led to the discovery of the interaction sites between the natively disordered GW182 silencing domain and the helical CNOT1(800-999) protein fragment, contributing to the understanding of the molecular mechanisms of recognition within protein complexes involved in gene silencing in different physiological processes.Niniejsza praca doktorska dotyczy biofizycznych podstaw oddziaływania między białkami zaangażowanymi w wyciszanie ekspresji genów przez mikro-RNA (miRNA), a mianowicie pomiędzy białkiem CNOT1 a domeną wyciszającą białka GW182. W procesie wyciszania ekspresji genów przez miRNA, cząsteczki te wiążą się z białkiem Argonaute i naprowadzają je na cząsteczkę mRNA, która ma ulec wyciszeniu. Z białkiem Argonaute oddziałuje białko GW182, które z kolei wiąże się z kompleksem deadenylaz CCR4-NOT. Kompleks ten deadenyluje mRNA oraz może także blokować jego translację, co łącznie prowadzi do wyciszenia ekspresji danego genu. Z kolei w wyciszaniu mRNA zawierających sekwencje bogate w adeninę i urydynę, rolę miRNA wraz z Argonaute i GW182 pełni białko o nazwie tristetraprolina, które odgrywa kluczową rolę w procesach odpowiedzi na stany zapalne. Oddziaływania pomiędzy składnikami tego skomplikowanego układu białek o wielkich masach cząsteczkowych są jeszcze stosunkowo słabo poznane. W szczególności, nieznane były miejsca odpowiedzialne za tworzenie kompleksu pomiędzy GW182 a CCR4-NOT. Doświadczenia z zakresu biologii molekularnej pozwoliły na identyfikację miejsc wiążących CCR4-NOT w sekwencji domeny wyciszającej białka GW182. Jedno z nich ma kluczowy wpływ na deadenylację, a drugie - kluczowy wpływ na oddziaływanie z kompleksem CCR4-NOT za pośrednictwem jego centralnej podjednostki CNOT1. Badania biofizyczne metodą wymiany wodór-deuter sprzężoną ze spektrometrią mas pozwoliły z kolei na identyfikację miejsca oddziaływania GW182 na białku CNOT1 (we fragmencie 800-999), które, niespodziewanie, okazało się bardzo dobrze pokrywać z miejscem oddziaływania CNOT1(800-999) z tristetraproliną. Eksperymenty biochemiczne wykazały, że białka te konkurują o miejsce oddziaływania na CNOT1(800-999). Białka GW182 i tristetraprolina oddziałują z CNOT1 wykorzystując ten sam motyw sekwencji, RLPXφ, w bardzo podobny, jednak nie identyczny sposób. Sekwencja ta prawdopodobnie działa jako tzw. krótki motyw liniowy (z ang. short linear motif, SLiM). Zatem te dwa szlaki kontroli nad ekspresją genów krzyżują się. W pracy zbadano także dynamikę strukturalną białka CNOT1(800-999) oraz domeny wyciszającej białka GW182. Wykazano eksperymentalnie, że białko GW182 ma nieustrukturyzowany charakter, oprócz domeny wiążącej RNA (RRM), która ma strukturę bardzo dynamiczną. Natomiast białko CNOT1(800-999) charakteryzuje się stabilną, ściśle upakowaną strukturą. Przeprowadzone badania doprowadziły do odkrycia miejsc oddziaływania pomiędzy natywnie nieustrukturyzowaną domeną wyciszającą GW182, a helikalnym fragmentem białka CNOT1(800 999), przyczyniając się do zrozumienia molekularnych mechanizmów rozpoznawania w kompleksach białkowych odpowiedzialnych za regulację ekspresji genów w różnych procesach komórkowych.
Book chapters on the topic "Domain-motif interaction"
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Littlewood, Trevor D., and Gerard I. Evan. "Introduction." In Helix-Loop-Helix Transcription Factors, 1–5. Oxford University PressOxford, 1998. http://dx.doi.org/10.1093/oso/9780198502487.003.0001.
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Abstract The transcription of genes within eukaryotic cells is controlled by complex interactions between transcription factors and specific DNA recognition sequences in target genes. These DNA-binding transcription factors fall into a number of groups, each defined by shared sequence and, presumably structural, motifs. One such motif is the helix-loop-helix (HLH), first identified in an immunoglobulin enhancer-binding polypeptide as well as several other proteins known, or suspected, to be transcription factors [741]. The HLH region has also sometimes been referred to as the ‘Myc homology domain’, doubtless in deference to the notoriety and perceived importance of Myc proteins in carcinogenesis. However, the HLH motif is present in many proteins of diverse biological function and unified only by their common involvement in transcriptional regulation (reviewed in [3, 4, 32, 34, 43, 51, 62, 64, 69, 1312]). The HLH domain is a dimerization domain that mediates homo- and/or hetero-dimerization with other HLH proteins. The HLH domain is usually adjacent to a short region of basic residues that constitutes the sequence-specific DNA interaction interface; hence such proteins are often referred to as bHLH proteins. A second group of bHLH proteins contains an additional dimerization domain, the leucine zipper [1148], immediately C-terminal to the HLH. These proteins are commonly referred to as bHLHZ proteins. Members of a third group of HLH proteins lack a functional DNA-binding domain and act as negative regulators of bHLH proteins.
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Pieler, Tomas. "Interaction of 5S RNA -with TFIIIA." In RNA-Protein Interactions, 178–91. Oxford University PressOxford, 1995. http://dx.doi.org/10.1093/oso/9780199635054.003.0008.
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Abstract Among the structural motifs which identify DNA- and RNA-binding proteins in eukaryotes, zinc finger modules are unique in defining the nucleic acid-binding domain in proteins with a demonstrated ability to form sequence-specific com plexes with either RNA or DNA or even with both classes of nucleic acids (1). Transcription factor IIIA (TFIIIA) is the founding member of the zinc finger protein superfamily, which is comprised of several hundred members in vertebrates (2, 3). TFIIIA is one of the most abundant proteins in immature Xenopus laevis oocytes, where it is found primarily in a complex with 5S ribosomal RNA (4). The key structural feature in TFIIIA comes from nine copies of a sequence motif that has been termed zinc finger, since two pairs of invariant cysteines and histidines mediate the three-dimensional (3-D) folding of two antiparallel !3-sheets and one a helical element, mainly by coordination of zinc (Figure 1). The zinc finger duster in TFIIIA is not only responsible for the specific recognition of 5S RNA, but also promotes sequence-specific binding to the internal control region of the 5S RNA gene, thereby defining the first step in the formation of an active transcription complex (5, 6).
Conference papers on the topic "Domain-motif interaction"
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Hongbiao Liu and J. Liu. "Prediction of Domain Interactive Motif Pairs." In 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference. IEEE, 2005. http://dx.doi.org/10.1109/iembs.2005.1616309.
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Borges, Heraldo, Antonio Castro, Rafaelli Coutinho, Fabio Porto, Esther Pacitti, and Eduardo Ogasawara. "STMotif Explorer: A Tool for Spatiotemporal Motif Analysis." In Anais Estendidos do Simpósio Brasileiro de Banco de Dados. Sociedade Brasileira de Computação - SBC, 2023. http://dx.doi.org/10.5753/sbbd_estendido.2023.233371.
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Pattern discovery is an important task in time series mining. A pattern that occurs a significant number of times in a time series is called a motif. Several approaches have been developed to discover motifs in time series. However, we can observe a clear gap in exploring the spatial-time series data. It is challenging to understand and characterize the meaning of the motif obtained concerning the data domain, comparing different approaches and analyzing the quality of the results obtained. We propose STMotif Explorer, a spatial-time motif analysis system that aims to interactively discover and visualize spatial-time motifs in different domains, offering insight to users. STMotif Explorer enables users to use and implement novel spatiotemporal motif detection techniques and then run this across various domains. Besides, STMotif Explorer offers the users a set of interactive resources where it is possible to visualize and analyze the discovered motifs and compare the results from different techniques. We show the features of our system with different approaches using real data.
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Cho, Hongkwan, Abdul Sheikh, and Daria A. Narmoneva. "Non-Specific Endothelial Cell Interactions With the Substrate Result in Cell Activation and Angiogenesis In Vitro." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19094.
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Vascularization is critical for success of tissue engineering applications. Previous studies by us and others have shown that self-assembling peptide nanoscaffold RAD16-II promotes de novo capillary formation (angiogenesis) in vitro and neovascularization in vivo, and is a promising material for tissue engineering applications [1, 2]. However, the molecular mechanisms for cell interactions with this material are not known. Angiogenesis is mediated via interactions between integrins, which are expressed on the surface of activated endothelial cells (ECs), and extracellular matrix proteins. Among several integrins, αvβ3 is the most abundant and influential receptor regulating angiogenesis [3]. The αvβ3 integrin binds to its ligands via Arg-Gly-Asp (RGD) biding motif. However, there are no RGD motifs on RAD 16-II peptide. Instead, it contains three RAD motifs. Studies have shown that non-specific binding of αvβ3 with RAD can be retained through R and D sides [4]. The objective of this study, therefore, is to elucidate the underlying molecular mechanisms of RAD16-II nanoscaffold interactions with microvascular endothelial cells. We hypothesize that non-specific interactions between RAD16-II peptide nanoscaffold and αvβ3 integrin result in phosphorylations of β3 cytoplasmic domain, which then activate downstream angiogenic signaling pathways and promote angiogenesis.