Articoli di riviste: "Acidic patch"

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Skrajna, Aleksandra, Dennis Goldfarb, Katarzyna M. Kedziora, Emily M. Cousins, Gavin D. Grant, Cathy J. Spangler, Emily H. Barbour et al. "Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding". Nucleic Acids Research 48, n. 17 (7 luglio 2020): 9415–32. http://dx.doi.org/10.1093/nar/gkaa544.

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Abstract Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that disrupts all exposed histone surfaces to comprehensively assess how proteins recognize nucleosomes. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk interactions, whereas nearly half of the nucleosome disk participates only minimally in protein binding. Our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly engages the acidic patch, and we elucidate a redundant mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub and establishes universal principles of nucleosome recognition.

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Cucinotta, Christine E., A. Elizabeth Hildreth, Brendan M. McShane, Margaret K. Shirra e Karen M. Arndt. "The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo". Nucleic Acids Research 47, n. 16 (21 giugno 2019): 8410–23. http://dx.doi.org/10.1093/nar/gkz549.

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Abstract The nucleosome core regulates DNA-templated processes through the highly conserved nucleosome acidic patch. While structural and biochemical studies have shown that the acidic patch controls chromatin factor binding and activity, few studies have elucidated its functions in vivo. We employed site-specific crosslinking to identify proteins that directly bind the acidic patch in Saccharomyces cerevisiae and demonstrated crosslinking of histone H2A to Paf1 complex subunit Rtf1 and FACT subunit Spt16. Rtf1 bound to nucleosomes through its histone modification domain, supporting its role as a cofactor in H2B K123 ubiquitylation. An acidic patch mutant showed defects in nucleosome positioning and occupancy genome-wide. Our results provide new information on the chromatin engagement of two central players in transcription elongation and emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.

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Kalashnikova, Anna A., Mary E. Porter-Goff, Uma M. Muthurajan, Karolin Luger e Jeffrey C. Hansen. "The role of the nucleosome acidic patch in modulating higher order chromatin structure". Journal of The Royal Society Interface 10, n. 82 (6 maggio 2013): 20121022. http://dx.doi.org/10.1098/rsif.2012.1022.

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Higher order folding of chromatin fibre is mediated by interactions of the histone H4 N-terminal tail domains with neighbouring nucleosomes. Mechanistically, the H4 tails of one nucleosome bind to the acidic patch region on the surface of adjacent nucleosomes, causing fibre compaction. The functionality of the chromatin fibre can be modified by proteins that interact with the nucleosome. The co-structures of five different proteins with the nucleosome (LANA, IL-33, RCC1, Sir3 and HMGN2) recently have been examined by experimental and computational studies. Interestingly, each of these proteins displays steric, ionic and hydrogen bond complementarity with the acidic patch, and therefore will compete with each other for binding to the nucleosome. We first review the molecular details of each interface, focusing on the key non-covalent interactions that stabilize the protein–acidic patch interactions. We then propose a model in which binding of proteins to the nucleosome disrupts interaction of the H4 tail domains with the acidic patch, preventing the intrinsic chromatin folding pathway and leading to assembly of alternative higher order chromatin structures with unique biological functions.

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Oleinikov, Pavel D., Anastasiia S. Fedulova, Grigoriy A. Armeev, Nikita A. Motorin, Lovepreet Singh-Palchevskaia, Anastasiia L. Sivkina, Pavel G. Feskin et al. "Interactions of Nucleosomes with Acidic Patch-Binding Peptides: A Combined Structural Bioinformatics, Molecular Modeling, Fluorescence Polarization, and Single-Molecule FRET Study". International Journal of Molecular Sciences 24, n. 20 (14 ottobre 2023): 15194. http://dx.doi.org/10.3390/ijms242015194.

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In eukaryotic organisms, genomic DNA associates with histone proteins to form nucleosomes. Nucleosomes provide a basis for genome compaction, epigenetic markup, and mediate interactions of nuclear proteins with their target DNA loci. A negatively charged (acidic) patch located on the H2A-H2B histone dimer is a characteristic feature of the nucleosomal surface. The acidic patch is a common site in the attachment of various chromatin proteins, including viral ones. Acidic patch-binding peptides present perspective compounds that can be used to modulate chromatin functioning by disrupting interactions of nucleosomes with natural proteins or alternatively targeting artificial moieties to the nucleosomes, which may be beneficial for the development of new therapeutics. In this work, we used several computational and experimental techniques to improve our understanding of how peptides may bind to the acidic patch and what are the consequences of their binding. Through extensive analysis of the PDB database, histone sequence analysis, and molecular dynamic simulations, we elucidated common binding patterns and key interactions that stabilize peptide–nucleosome complexes. Through MD simulations and FRET measurements, we characterized changes in nucleosome dynamics conferred by peptide binding. Using fluorescence polarization and gel electrophoresis, we evaluated the affinity and specificity of the LANA1-22 peptide to DNA and nucleosomes. Taken together, our study provides new insights into the different patterns of intermolecular interactions that can be employed by natural and designed peptides to bind to nucleosomes, and the effects of peptide binding on nucleosome dynamics and stability.

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Navarro Negredo, Paloma, James R. Edgar, Antoni G. Wrobel, Nathan R. Zaccai, Robin Antrobus, David J. Owen e Margaret S. Robinson. "Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting". Journal of Cell Biology 216, n. 9 (25 luglio 2017): 2927–43. http://dx.doi.org/10.1083/jcb.201602058.

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Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell.

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Debelouchina, Galia T., Karola Gerecht e Tom W. Muir. "Ubiquitin utilizes an acidic surface patch to alter chromatin structure". Nature Chemical Biology 13, n. 1 (21 novembre 2016): 105–10. http://dx.doi.org/10.1038/nchembio.2235.

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Birrane, Gabriel, Anne P. Beigneux, Brian Dwyer, Bettina Strack-Logue, Kristian Kølby Kristensen, Omar L. Francone, Loren G. Fong et al. "Structure of the lipoprotein lipase–GPIHBP1 complex that mediates plasma triglyceride hydrolysis". Proceedings of the National Academy of Sciences 116, n. 5 (17 dicembre 2018): 1723–32. http://dx.doi.org/10.1073/pnas.1817984116.

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Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive. Inspired by our recent discovery that GPIHBP1’s acidic domain preserves LPL structure and activity, we crystallized an LPL–GPIHBP1 complex and solved its structure. GPIHBP1’s LU domain binds to LPL’s C-terminal domain, largely by hydrophobic interactions. Analysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-terminal domains. GPIHBP1’s acidic domain was not defined in the electron density map but was positioned to interact with LPL’s large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL. The LPL–GPIHBP1 structure provides insights into mutations causing chylomicronemia.

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Batchelor, Lucinda K., Louis De Falco, Paul J. Dyson e Curtis A. Davey. "Viral peptide conjugates for metal-warhead delivery to chromatin". RSC Advances 14, n. 13 (2024): 8718–25. http://dx.doi.org/10.1039/d4ra01617c.

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CROWLEY, Peter B., David M. HUNTER, Katsuko SATO, William McFARLANE e Christopher DENNISON. "The parsley plastocyanin-turnip cytochrome f complex: a structurally distorted but kinetically functional acidic patch". Biochemical Journal 378, n. 1 (15 febbraio 2004): 45–51. http://dx.doi.org/10.1042/bj20031423.

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In general, inter-protein electron transfer proceeds via the formation of transient complexes. The initial stage of the interaction between plastocyanin (PCu) and cytochrome f (cyt f) from plants is mediated by complementary electrostatics. Given the diffuse nature of its acidic patch, parsley PCu is an atypical example of a plant PCu. The interaction of this PCu with turnip cyt f was investigated by stopped-flow kinetics, NMR spectroscopy and protein-docking simulations. We show that, despite the altered acidic patch, parsley PCu is as efficient as spinach PCu in accepting electrons from cyt f, over the physiological range of ionic strength. At high ionic strength, the rate constant for the reaction of cyt f with parsley PCu is twice that of the spinach protein. This difference in reactivity is attributed to variations in the hydrophobic patch of parsley PCu. The results of NMR studies and protein-docking simulations indicate that parsley PCu and its spinach analogue adopt different orientations in their complexes with cyt f.

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Haneburger, Ina, Andreas Eichinger, Arne Skerra e Kirsten Jung. "New Insights into the Signaling Mechanism of the pH-responsive, Membrane-integrated Transcriptional Activator CadC of Escherichia coli". Journal of Biological Chemistry 286, n. 12 (6 gennaio 2011): 10681–89. http://dx.doi.org/10.1074/jbc.m110.196923.

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The membrane-integrated transcriptional regulator CadC of Escherichia coli activates expression of the cadBA operon at low external pH with concomitantly available lysine, providing adaptation to mild acidic stress. CadC is a representative of the ToxR-like proteins that combine sensory, signal transduction, and DNA-binding activities within a single polypeptide. Although several ToxR-like regulators such as CadC, as well as the main regulator of Vibrio cholerae virulence, ToxR itself, which activate gene expression at acidic pH, have been intensively investigated, their molecular activation mechanism is still unclear. In this study, a structure-guided mutational analysis was performed to elucidate the mechanism by which CadC detects acidification of the external milieu. Thus, a cluster of negatively charged amino acids (Asp-198, Asp-200, Glu-461, Glu-468, and Asp-471) was found to be crucial for pH detection. These amino acids form a negatively charged patch on the surface of the periplasmic domain of CadC that stretches across its two subdomains. The results of different combinations of amino acid replacements within this patch indicated that the N-terminal subdomain integrates and transduces the signals coming from both subdomains to the transmembrane domain. Alterations in the phospholipid composition did not influence pH-dependent cadBA expression, and therefore, interplay of the acidic surface patch with the negatively charged headgroups is unlikely. Models are discussed according to which protonation of these acidic amino acid side chains reduces repulsive forces between the two subdomains and/or between two monomers within a CadC dimer and thereby enables receptor activation upon lowering of the environmental pH.

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Guiney, Evan L., Till Klecker e Scott D. Emr. "Identification of the endocytic sorting signal recognized by the Art1-Rsp5 ubiquitin ligase complex". Molecular Biology of the Cell 27, n. 25 (15 dicembre 2016): 4043–54. http://dx.doi.org/10.1091/mbc.e16-08-0570.

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Targeted endocytosis of plasma membrane (PM) proteins allows cells to adjust their complement of membrane proteins to changing extracellular conditions. For a wide variety of PM proteins, initiation of endocytosis is triggered by ubiquitination. In yeast, arrestin-related trafficking adaptors (ARTs) enable a single ubiquitin ligase, Rsp5, to specifically and selectively target a wide range of PM proteins for ubiquitination and endocytosis. However, the mechanisms that allow ARTs to specifically recognize their appropriate substrates are unknown. We present the molecular features in the methionine permease Mup1 that are required for Art1-Rsp5–mediated ubiquitination and endocytosis. A combination of genetics, fluorescence microscopy, and biochemistry reveals three critical features that comprise an ART sorting signal in the Mup1 N-terminal cytosolic tail: 1) an extended acidic patch, 2) in close proximity to the first Mup1 transmembrane domain, and 3) close to the ubiquitinated lysines. We show that a functionally similar ART sorting signal is also required for the endocytosis of a second Art1-dependent cargo, Can1, suggesting a common mechanism for recognition of Art1 substrates. We isolate two separate suppressor mutations in the Art1 C-terminal domain that allele-specifically restore endocytosis of two Mup1 acidic patch mutants, consistent with an interaction between the Art1 C-terminus and the Mup1 acidic patch. We propose that this interaction is required for recruitment of the Art1-Rsp5 ubiquitination complex.

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Nakabayashi, Yu, e Masayuki Seki. "Functional Analyses of an Evolutionarily Conserved Acidic Patch on the Nucleosome". Biological and Pharmaceutical Bulletin 46, n. 11 (1 novembre 2023): 1619–24. http://dx.doi.org/10.1248/bpb.b23-00480.

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Kujirai, Tomoya, Christian Zierhut, Yoshimasa Takizawa, Ryan Kim, Lumi Negishi, Nobuki Uruma, Seiya Hirai, Hironori Funabiki e Hitoshi Kurumizaka. "Structural basis for the inhibition of cGAS by nucleosomes". Science 370, n. 6515 (10 settembre 2020): 455–58. http://dx.doi.org/10.1126/science.abd0237.

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The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) senses invasion of pathogenic DNA and stimulates inflammatory signaling, autophagy, and apoptosis. Organization of host DNA into nucleosomes was proposed to limit cGAS autoinduction, but the underlying mechanism was unknown. Here, we report the structural basis for this inhibition. In the cryo–electron microscopy structure of the human cGAS–nucleosome core particle (NCP) complex, two cGAS monomers bridge two NCPs by binding the acidic patch of the histone H2A-H2B dimer and nucleosomal DNA. In this configuration, all three known cGAS DNA binding sites, required for cGAS activation, are repurposed or become inaccessible, and cGAS dimerization, another prerequisite for activation, is inhibited. Mutating key residues linking cGAS and the acidic patch alleviates nucleosomal inhibition. This study establishes a structural framework for why cGAS is silenced on chromatinized self-DNA.

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Ho, Cheng-Han, Yoshimasa Takizawa, Wataru Kobayashi, Yasuhiro Arimura, Hiroshi Kimura e Hitoshi Kurumizaka. "Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase". Life Science Alliance 4, n. 4 (11 febbraio 2021): e202000919. http://dx.doi.org/10.26508/lsa.202000919.

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SET8 is solely responsible for histone H4 lysine-20 (H4K20) monomethylation, which preferentially occurs in nucleosomal H4. However, the underlying mechanism by which SET8 specifically promotes the H4K20 monomethylation in the nucleosome has not been elucidated. Here, we report the cryo-EM structures of the human SET8–nucleosome complexes with histone H3 and the centromeric H3 variant, CENP-A. Surprisingly, we found that the overall cryo-EM structures of the SET8–nucleosome complexes are substantially different from the previous crystal structure models. In the complexes with H3 and CENP-A nucleosomes, SET8 specifically binds the nucleosomal acidic patch via an arginine anchor, composed of the Arg188 and Arg192 residues. Mutational analyses revealed that the interaction between the SET8 arginine anchor and the nucleosomal acidic patch plays an essential role in the H4K20 monomethylation activity. These results provide the groundwork for understanding the mechanism by which SET8 specifically accomplishes the H4K20 monomethylation in the nucleosome.

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Lesbats, Paul, Erik Serrao, Daniel P. Maskell, Valerie E. Pye, Nicola O’Reilly, Dirk Lindemann, Alan N. Engelman e Peter Cherepanov. "Structural basis for spumavirus GAG tethering to chromatin". Proceedings of the National Academy of Sciences 114, n. 21 (10 maggio 2017): 5509–14. http://dx.doi.org/10.1073/pnas.1621159114.

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The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A–H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor residue in GAG result in global redistribution of PFV and macaque simian foamy virus (SFVmac) integration sites toward centromeres, dampening the resulting proviral expression without affecting the overall efficiency of integration. Our findings underscore the importance of retroviral structural proteins for integration site selection and the avoidance of genomic junkyards.

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Gallego, Laura D., Medini Ghodgaonkar Steger, Anton A. Polyansky, Tobias Schubert, Bojan Zagrovic, Ning Zheng, Tim Clausen, Franz Herzog e Alwin Köhler. "Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6–Bre1". Proceedings of the National Academy of Sciences 113, n. 38 (6 settembre 2016): 10553–58. http://dx.doi.org/10.1073/pnas.1606863113.

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Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6–Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch. By docking onto the NCP surface in this distinct orientation, Bre1 positions the Rad6 active site directly over H2B Lys123. The Spt–Ada–Gcn5 acetyltransferase (SAGA) H2B deubiquitinase module competes with Bre1 for binding to the NCP acidic patch, indicating regulatory control. Our study reveals a mechanism that ensures site-specific NCP ubiquitination and fine-tuning of opposing enzymatic activities.

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Dao, Hai T., Barbara E. Dul, Geoffrey P. Dann, Glen P. Liszczak e Tom W. Muir. "A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing". Nature Chemical Biology 16, n. 2 (9 dicembre 2019): 134–42. http://dx.doi.org/10.1038/s41589-019-0413-4.

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Sato, Katsuko, Takamitsu Kohzuma e Christopher Dennison. "Pseudospecificity of the Acidic Patch of Plastocyanin for the Interaction with Cytochromef". Journal of the American Chemical Society 126, n. 10 (marzo 2004): 3028–29. http://dx.doi.org/10.1021/ja038188k.

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Bortoluzzi, Alessio, Anastasia Amato, Xavier Lucas, Manuel Blank e Alessio Ciulli. "Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains". Biochemical Journal 474, n. 10 (4 maggio 2017): 1633–51. http://dx.doi.org/10.1042/bcj20161053.

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The plant homeodomain (PHD) fingers are among the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation; however, less is known about the recognition of secondary structure features within the histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A [BAZ2A, also known as TIP5 (TTF-I/interacting protein 5)] in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name ‘acidic wall’, found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or destabilization of H3 helicity. Our work unravels the structural basis for binding of the helical H3 tail by PHD fingers and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes.

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Zhu, Michael X. "A well-known potassium channel plays a critical role in lysosomes". Journal of Cell Biology 216, n. 6 (16 maggio 2017): 1513–15. http://dx.doi.org/10.1083/jcb.201704017.

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Whole-endolysosome patch clamping presents new opportunities to identify and characterize channels pivotal for these acidic organelles. In this issue (Wang et al., 2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612123), the identification of a role for the large conductance calcium-activated potassium channel brings new thinking about regulation of lysosome membrane potential and function.

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Lehmann, Laura C., Luka Bacic, Graeme Hewitt, Klaus Brackmann, Anton Sabantsev, Guillaume Gaullier, Sofia Pytharopoulou et al. "Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch". Cell Reports 33, n. 12 (dicembre 2020): 108529. http://dx.doi.org/10.1016/j.celrep.2020.108529.

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Wong, Won Fen, Kuan Ping Ang, Gautam Sethi e Chung Yeng Looi. "Recent Advancement of Medical Patch for Transdermal Drug Delivery". Medicina 59, n. 4 (17 aprile 2023): 778. http://dx.doi.org/10.3390/medicina59040778.

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Transdermal patches are a non-invasive method of drug administration. It is an adhesive patch designed to deliver a specific dose of medication through the skin and into the bloodstream throughout the body. Transdermal drug delivery has several advantages over other routes of administration, for instance, it is less invasive, patient-friendly, and has the ability to bypass first-pass metabolism and the destructive acidic environment of the stomach that occurs upon the oral ingestion of drugs. For decades, transdermal patches have attracted attention and were used to deliver drugs such as nicotine, fentanyl, nitroglycerin, and clonidine to treat various diseases or conditions. Recently, this method is also being explored as a means of delivering biologics in various applications. Here, we review the existing literatures on the design and usage of medical patches in transdermal drug delivery, with a focus on the recent advances in innovation and technology that led to the emergence of smart, dissolvable/biodegradable, and high-loading/release, as well as 3D-printed patches.

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McBride, Matthew J., Nazar Mashtalir, Evan B. Winter, Hai T. Dao, Martin Filipovski, Andrew R. D’Avino, Hyuk-Soo Seo et al. "The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma". Nature Structural & Molecular Biology 27, n. 9 (3 agosto 2020): 836–45. http://dx.doi.org/10.1038/s41594-020-0466-9.

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AbstractInteractions between chromatin-associated proteins and the histone landscape play major roles in dictating genome topology and gene expression. Cancer-specific fusion oncoproteins, which display unique chromatin localization patterns, often lack classical DNA-binding domains, presenting challenges in identifying mechanisms governing their site-specific chromatin targeting and function. Here we identify a minimal region of the human SS18-SSX fusion oncoprotein (the hallmark driver of synovial sarcoma) that mediates a direct interaction between the mSWI/SNF complex and the nucleosome acidic patch. This binding results in altered mSWI/SNF composition and nucleosome engagement, driving cancer-specific mSWI/SNF complex targeting and gene expression. Furthermore, the C-terminal region of SSX confers preferential affinity to repressed, H2AK119Ub-marked nucleosomes, underlying the selective targeting to polycomb-marked genomic regions and synovial sarcoma–specific dependency on PRC1 function. Together, our results describe a functional interplay between a key nucleosome binding hub and a histone modification that underlies the disease-specific recruitment of a major chromatin remodeling complex.

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Sato, Shoko, Yoshimasa Takizawa, Fumika Hoshikawa, Mariko Dacher, Hiroki Tanaka, Hiroaki Tachiwana, Tomoya Kujirai et al. "Cryo-EM structure of the nucleosome core particle containing Giardia lamblia histones". Nucleic Acids Research 49, n. 15 (5 agosto 2021): 8934–46. http://dx.doi.org/10.1093/nar/gkab644.

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Abstract Giardia lamblia is a pathogenic unicellular eukaryotic parasite that causes giardiasis. Its genome encodes the canonical histones H2A, H2B, H3, and H4, which share low amino acid sequence identity with their human orthologues. We determined the structure of the G. lamblia nucleosome core particle (NCP) at 3.6 Å resolution by cryo-electron microscopy. G. lamblia histones form a characteristic NCP, in which the visible 125 base-pair region of the DNA is wrapped in a left-handed supercoil. The acidic patch on the G. lamblia octamer is deeper, due to an insertion extending the H2B α1 helix and L1 loop, and thus cannot bind the LANA acidic patch binding peptide. The DNA and histone regions near the DNA entry-exit sites could not be assigned, suggesting that these regions are asymmetrically flexible in the G. lamblia NCP. Characterization by thermal unfolding in solution revealed that both the H2A–H2B and DNA association with the G. lamblia H3–H4 were weaker than those for human H3–H4. These results demonstrate the uniformity of the histone octamer as the organizing platform for eukaryotic chromatin, but also illustrate the unrecognized capability for large scale sequence variations that enable the adaptability of histone octamer surfaces and confer internal stability.

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Dhar, Surbhi, Ozge Gursoy-Yuzugullu, Ramya Parasuram e Brendan D. Price. "The tale of a tail: histone H4 acetylation and the repair of DNA breaks". Philosophical Transactions of the Royal Society B: Biological Sciences 372, n. 1731 (28 agosto 2017): 20160284. http://dx.doi.org/10.1098/rstb.2016.0284.

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The ability of cells to detect and repair DNA double-strand breaks (DSBs) within the complex architecture of the genome requires co-ordination between the DNA repair machinery and chromatin remodelling complexes. This co-ordination is essential to process damaged chromatin and create open chromatin structures which are required for repair. Initially, there is a PARP-dependent recruitment of repressors, including HP1 and several H3K9 methyltransferases, and exchange of histone H2A.Z by the NuA4-Tip60 complex. This creates repressive chromatin at the DSB in which the tail of histone H4 is bound to the acidic patch on the nucleosome surface. These repressor complexes are then removed, allowing rapid acetylation of the H4 tail by Tip60. H4 acetylation blocks interaction between the H4 tail and the acidic patch on adjacent nucleosomes, decreasing inter-nucleosomal interactions and creating open chromatin. Further, the H4 tail is now free to recruit proteins such as 53BP1 to DSBs, a process modulated by H4 acetylation, and provides binding sites for bromodomain proteins, including ZMYND8 and BRD4, which are important for DSB repair. Here, we will discuss how the H4 tail functions as a dynamic hub that can be programmed through acetylation to alter chromatin packing and recruit repair proteins to the break site. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

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Ubbink, M., X. S. Gong, J. C. Gray e D. S. Bendall. "Protein:protein interactions studied by NMR: does cytochrome c bind to plastocyanin on its acidic patch?" Journal of Inorganic Biochemistry 59, n. 2-3 (agosto 1995): 282. http://dx.doi.org/10.1016/0162-0134(95)97385-4.

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Subramanian, Vidya, Aprotim Mazumder, Lauren E. Surface, Vincent L. Butty, Paul A. Fields, Allison Alwan, Lillian Torrey et al. "H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation". PLoS Genetics 9, n. 8 (22 agosto 2013): e1003725. http://dx.doi.org/10.1371/journal.pgen.1003725.

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Shaytan, Alexey, Grigoriy A. Armeev, Pavel D. Oleinikov, Nikita A. Motorin, Lavprit Singh-Palchevskaya, Anastasiia L. Sivkina, Pavel G. Feskin et al. "Interactions of nucleosomes with acidic patch binding peptides: Combining structural analysis, MD simulations, and experiments". Biophysical Journal 123, n. 3 (febbraio 2024): 3a. http://dx.doi.org/10.1016/j.bpj.2023.11.150.

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Wu, Yinsheng, Haoshen Xue, Fei Liu, Xinyue Wang, Ling Chen, Maoshen Chen, Bor-Sen Chiou, Xinghu Zhou, Xue Jiao e Fang Zhong. "Improving stability of phycocyanin under acidic conditions by surface patch binding induced complexation with gelatin". Food Hydrocolloids 161 (aprile 2025): 110876. http://dx.doi.org/10.1016/j.foodhyd.2024.110876.

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Evlanenkov, Konstantin K., Maxim V. Nikolaev, Natalia N. Potapieva, Konstantin V. Bolshakov e Denis B. Tikhonov. "Probing the Proton-Gated ASIC Channels Using Tetraalkylammonium Ions". Biomolecules 13, n. 11 (8 novembre 2023): 1631. http://dx.doi.org/10.3390/biom13111631.

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Abstract (sommario):

The action of tetraalkylammonium ions, from tetrametylammonium (TMA) to tetrapentylammonium (TPtA), on the recombinant and native acid-sensing ion channels (ASICs) was studied using the patch-clamp approach. The responses of ASIC1a, ASIC2a, and native heteromeric ASICs were inhibited by TPtA. The peak currents through ASIC3 were unaffected, whereas the steady-state currents were significantly potentiated. This effect was characterized by an EC50 value of 1.22 ± 0.12 mM and a maximal effect of 3.2 ± 0.5. The effects of TPtA were voltage-independent but significantly decreased under conditions of strong acidification, which caused saturation of ASIC responses. Molecular modeling predicted TPtA binding in the acidic pocket of closed ASICs. Bound TPtA can prevent acidic pocket collapse through a process involving ASIC activation and desensitization. Tetraethylammonium (TEA) inhibited ASIC1a and native ASICs. The effect was independent of the activating pH but decreased with depolarization, suggesting a pore-blocking mechanism.

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Merchant, Mark, Felix F. Vajdos, Mark Ultsch, Henry R. Maun, Ulrich Wendt, Jennifer Cannon, William Desmarais, Robert A. Lazarus, Abraham M. de Vos e Frederic J. de Sauvage. "Suppressor of Fused Regulates Gli Activity through a Dual Binding Mechanism". Molecular and Cellular Biology 24, n. 19 (1 ottobre 2004): 8627–41. http://dx.doi.org/10.1128/mcb.24.19.8627-8641.2004.

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ABSTRACT The Hedgehog pathway drives proliferation and differentiation by activating the Gli/Ci family of zinc finger transcription factors. Gli/Ci proteins form Hedgehog signaling complexes with other signaling components, including the kinesin-like protein Costal-2, the serine-threonine kinase Fused, and Suppressor of Fused [Su(fu)]. In these complexes Gli/Ci proteins are regulated by cytoplasmic sequestration, phosphorylation, and proteolysis. Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1. Furthermore, we have solved the crystal structure of the amino-terminal domain of human Su(fu)27-268 at 2.65 Å resolution. This domain forms a concave pocket with a prominent acidic patch. Mutation at Asp159 in the acidic patch disrupts Gli1 tethering and repression while not strongly disrupting binding, indicating that the amino-terminal domain of Su(fu) likely impacts Gli binding through a mechanism distinct from that for tethering and repression. These studies provide a structural basis for understanding the function of Su(fu).

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Guce, Abigail, Sarah Mortimer, Elizabeth Mellins, Lars Karlsson e Lawrence Stern. "Structural basis of HLA-DO inhibition of HLA-DM catalyzed peptide exchange on MHC class II (100.53)". Journal of Immunology 186, n. 1_Supplement (1 aprile 2011): 100.53. http://dx.doi.org/10.4049/jimmunol.186.supp.100.53.

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Abstract HLA-DO (DO) is a non-polymorphic, non-classical MHC class II molecule that localizes to the lysosome with HLA-DM (DM). DO is known to inhibit MHC class II peptide loading mediated by DM. The mechanism of inhibition by DO as well as the interactions between DO and DM remain unknown. Here, we present the three-dimensional structure of the DM and DO complex determined by x-ray crystallography at 3.2 Å resolution which is also the first resolved structure of DO. DO exhibits close structural similarity to the MHC class II molecule, HLA-DR (DR), with an rmsd of 0.8 Å2 despite only 25% sequence homology.The crystal complex shows DO residues mainly at the N-terminal side of the α1 peptide-binding groove interact with DM residues located at a concave surface. Some interactions are also observed involving DO residues from the IgG-like domain . DM concave surface includes an acidic patch where residues in and surrounding this acidic patch and residues in the IgG-like domain interact with DO. Interestingly, the interaction surface on DM to DO is spatially close to DM’s interaction surface for DR that was suggested by molecular modeling and mutagenesis studies. The novel structure of the DM/DO complex presented here provides an insight on the possible mechanism of inhibition of DO on DM as well as the mechanism of how DM catalyzes peptide loading to peptide free DR.

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Cucinotta, Christine E., Alexandria N. Young, Kristin M. Klucevsek e Karen M. Arndt. "The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae". PLOS Genetics 11, n. 8 (4 agosto 2015): e1005420. http://dx.doi.org/10.1371/journal.pgen.1005420.

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Valencia, Alfredo M., Clayton K. Collings, Hai T. Dao, Roodolph St. Pierre, Yung-Chih Cheng, Junwei Huang, Zhen-Yu Sun et al. "Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling". Cell 179, n. 6 (novembre 2019): 1342–56. http://dx.doi.org/10.1016/j.cell.2019.10.044.

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Leung, Justin W., Poonam Agarwal, Marella D. Canny, Fade Gong, Aaron D. Robison, Ilya J. Finkelstein, Daniel Durocher e Kyle M. Miller. "Nucleosome Acidic Patch Promotes RNF168- and RING1B/BMI1-Dependent H2AX and H2A Ubiquitination and DNA Damage Signaling". PLoS Genetics 10, n. 3 (6 marzo 2014): e1004178. http://dx.doi.org/10.1371/journal.pgen.1004178.

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36

Yu, Y., N. N. Jiménez-Vargas, C. D. Lopez Lopez, J. O. Jaramillo Polanco, N. W. Bunnett e S. Vanner. "A213 A NOVEL PH-SENSITIVE OPIOID ANALGESIC THAT IS SELECTIVELY ACTIVATED IN ACIDIC INFLAMMATORY ENVIRONMENTS". Journal of the Canadian Association of Gastroenterology 3, Supplement_1 (febbraio 2020): 85–87. http://dx.doi.org/10.1093/jcag/gwz047.212.

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Abstract Background Opioids drugs are effective analgesics for inflammatory disorders such as inflammatory bowel disease (IBD) but their effects at non-inflammed sites can cause serious morbidity and even death. Exploiting the knowledge that tissue pH in inflamed tissues is acidic (e.g. 6.5–7.0), a novel opioid analgesic, ±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenylpropionamide (NFEPP), with a low acid dissociation constant, was developed that selectively activates peripheral µ-opioid receptor (MOPr) at acidic pH. Thus, pH-sensitive binding of NFEPP could selectively inhibit nociceptive nerves in the inflamed colon and have no effect on non-inflamed tissues outside the GI tract. Aims Evaluate whether NFEPP causes inhibition of colonic nociceptors at acidic pH’s, which mimic the inflamed colon. Methods To evaluate pH sensitive property of NFEPP to activate MOPr, dorsal root ganglia (DRG) neurons from C57BL/6 mice were exposed to the MOPr agonists NFEPP (300nM, 15 min) or DAMGO (100nM, 15 min) or vehicle at pH 6.5 or 6.8 or 7.4. Neuronal excitability was measured by recording the rheobase (minimum current to fire an action potential) using patch clamp recordings of isolated dorsal root ganglia neurons. In parallel ex vivo studies of mouse colon, extracellular recordings were obtained from afferent nerves innervating the distal colon. Afferent responses to probing with von Frey hair (1 gm) were examined before and after exposure to NFEPP (300nM, 5 min superfusion) at pH 6.5 and 7.4 respectively. Oneway ANOVA and post hoc Dunnett and Bonferroni tests were used to analyze the data. Results In patch clamp studies, NFEPP caused a decrease in DRG excitability at pH 6.5 and 6.8 (increased rheobase 21.3%, p<0.05 and 28.9%, p<0.05 respectively compared to vehicle) but had no effect at physiological pH 7.4. DAMGO, a MOPr agonist, caused inhibition of nociceptor excitability at pH 7.4 (increased rheobase 25.2%, p<0.05 compared to vehicle) as shown in previous experiments, but had no effect at pH 6.5 and 6.8. Vehicle had no effect at the different pH’s. In colonic afferent nerve recordings, NFEPP significantly attenuated afferent response (28.9% P<0.01) to probing at pH 6.5 and this effect was reversed after a 15 min washout. At pH 7.4 NFEPP had no effect on afferent nerve firing. Conclusions NFEPP activated MOPr at acidic pH causing inhibition of colonic nociceptors. This pH-selective agonist provides a new strategy to relieve pain at the site of inflammation while being devoid of any of unwanted activity in non-inflamed organs. Funding Agencies CCC

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Hodges, Amelia J., Lisa M. Gloss e John J. Wyrick. "Residues in the Nucleosome Acidic Patch Regulate Histone Occupancy and Are Important for FACT Binding in Saccharomyces cerevisiae". Genetics 206, n. 3 (3 maggio 2017): 1339–48. http://dx.doi.org/10.1534/genetics.117.201939.

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Chen, Qinming, Renliang Yang, Nikolay Korolev, Chuan Fa Liu e Lars Nordenskiöld. "Regulation of Nucleosome Stacking and Chromatin Compaction by the Histone H4 N-Terminal Tail–H2A Acidic Patch Interaction". Journal of Molecular Biology 429, n. 13 (giugno 2017): 2075–92. http://dx.doi.org/10.1016/j.jmb.2017.03.016.

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Yakushiji, Fumika, Aoi Ishikawa, Akira Katsuyama e Satoshi Ichikawa. "Development of cyclic peptide derivatives from the N-terminal region of LANA for targeting the nucleosome acidic patch". Bioorganic & Medicinal Chemistry Letters 30, n. 2 (gennaio 2020): 126839. http://dx.doi.org/10.1016/j.bmcl.2019.126839.

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Pathak, Prasad, e Stephen Whalen. "Using Geospatial Techniques to Analyze Landscape Factors Controlling Ionic Composition of Arctic Lakes, Toolik Lake Region, Alaska". International Journal of Applied Geospatial Research 3, n. 3 (luglio 2012): 37–57. http://dx.doi.org/10.4018/jagr.2012070103.

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The impacts of climate change on landscapes in arctic Alaska are evident in terms of permafrost melting, frequent thermokarst activity, and the occurrence of more broadleaf vegetation. These changes may alter natural biogeochemical cycles of ions along with major nutrients and affect ionic compositions of lakes, as they are connected with the landscapes. However, the nature of the connectivity between lakes and landscapes in this region is not yet explored. The authors propose that geospatial analysis of landscape properties along with observed lake ion concentrations will enable an understanding of the currently existing landscape controls over ion inputs into the lakes. For the watersheds of 41 lakes in the Arctic Foothills region of Alaska, spatial properties of natural vegetation communities expressed in terms of percentage, shape complexity, and patch density metrics were derived using satellite data. Regression analyses were performed for concentration of ions as well as conductivity in lake water where the spatial metrics along with lake physical properties, lake order, and glacial till age categories were used as predicting variables in the regression. Landscape metrics for major land covers i.e., Percentage of Moist Acidic Tundra (MAT) and Moist Non-acidic Tundra (MNT) were the major predicting variables for concentration of several ions.

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Miller, Gregory J., Stanley D. Dunn e Eric H. Ball. "Interaction of the N- and C-terminal Domains of Vinculin". Journal of Biological Chemistry 276, n. 15 (21 dicembre 2000): 11729–34. http://dx.doi.org/10.1074/jbc.m008646200.

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The vinculin head to tail intramolecular self-association controls its binding sites for other components of focal adhesions. To study this interaction, the head and tail domains were expressed, purified, and assayed for various characteristics of complex formation. Analytical centrifugation demonstrated a strong interaction in solution and formation of a complex more asymmetric than either of the individual domains. A survey of binding conditions using a solid-phase binding assay revealed characteristics of both electrostatic and hydrophobic forces involved in the binding. In addition, circular dichroism of the individual domains and the complex demonstrated that conformational changes likely occur in both domains during association. The interaction sites were more closely mapped on the protein sequence by deletion mutagenesis. Amino acids 181–226, a basic region within the acidic head domain, were identified as a binding site for the vinculin tail, and residues 1009–1066 were identified as sufficient for binding the head. Moreover, mutation of an acidic patch in the tail (residues 1013–1015) almost completely eliminated its ability to interact with the head domain further supporting the significance of ionic interactions in the binding. Our data indicate that the interaction between the head and tail domains of vinculin occurs through oppositely charged contact sites and results in conformational changes in both domains.

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Georgiev, Yordan N., Manol H. Ognyanov, Hiroaki Kiyohara, Tsvetelina G. Batsalova, Balik M. Dzhambazov, Milan Ciz, Petko N. Denev et al. "Acidic polysaccharide complexes from purslane, silver linden and lavender stimulate Peyer’s patch immune cells through innate and adaptive mechanisms". International Journal of Biological Macromolecules 105 (dicembre 2017): 730–40. http://dx.doi.org/10.1016/j.ijbiomac.2017.07.095.

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Al Hanbali, Othman A., Haji Muhammad Shoaib Khan, Muhammad Sarfraz, Mosab Arafat, Shakeel Ijaz e Abdul Hameed. "Transdermal patches: Design and current approaches to painless drug delivery". Acta Pharmaceutica 69, n. 2 (1 giugno 2019): 197–215. http://dx.doi.org/10.2478/acph-2019-0016.

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Abstract Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.

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Marcianò, G., e D. T. Huang. "Structure of the human histone chaperone FACT Spt16 N-terminal domain". Acta Crystallographica Section F Structural Biology Communications 72, n. 2 (22 gennaio 2016): 121–28. http://dx.doi.org/10.1107/s2053230x15024565.

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The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of theSaccharomyces cerevisiaeandSchizosaccharomyces pombeSpt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.

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Bociąg, Katarzyna. "The impact of acidic organie Matter on the diversity of underwater vegetation in soft water lakes". Acta Societatis Botanicorum Poloniae 72, n. 3 (2011): 221–29. http://dx.doi.org/10.5586/asbp.2003.029.

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This paper addresses underwater vegetation in soft water lakes which are influenced by the anthropogenic input of allochtonic dissolved organic matter (DOM) from drained bogs. The aim of this work is to test the hypothesis regarding the role of DOM in shaping the diversity of underwater vegetation. Large differences in underwater vegetation habitats, the limitation of their occurrence to increasingly shallower littoral (the depth of the lower limit of their occurrence decreased from 12 m up to 1 m) and the regression of underwater vegetation were observed in lake types ranging from oligohumic (median (Me) of DOC in water = 2.5 mg C dm<sup>-3</sup>) to polyhumic (Me of DOC = 35.6 mg C dm<sup>-3</sup>). The gradual simplification of internal plant patch structure occurred and the Shannon-Weaver diversity index decreased (Me 0.04 → 0.00). Fewer species were observed in the lakes (Me 9 → 2), and the underwater vegetation covered increasingly smaller areas. Species replacement did not occur and no invasive species appeared.

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Huang, Ren-Qi, e Glenn H. Dillon. "Effect of Extracellular pH on GABA-Activated Current in Rat Recombinant Receptors and Thin Hypothalamic Slices". Journal of Neurophysiology 82, n. 3 (1 settembre 1999): 1233–43. http://dx.doi.org/10.1152/jn.1999.82.3.1233.

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We studied the effects of extracellular pH (pHo) on γ-aminobutyric acid (GABA)–mediated Cl− current in rat hypothalamic neurons and recombinant type-A GABA (GABAA) receptors stably expressed in human embryonic kidney cells (HEK 293), using whole cell and outside-out patch-clamp recordings. In α3β2γ2s receptors, acidic pH decreased, whereas alkaline pH increased the response to GABA in a reversible and concentration-dependent manner. Acidification shifted the GABA concentration-response curve to the right, significantly increasing the EC50 for GABA without appreciably changing the slope or maximal current induced by GABA. We obtained similar effects of pH in α1β2γ2 receptors and in GABA-activated currents recorded from thin hypothalamic brain slices. In outside-out patches recorded from α3β2γ2 recombinant receptors, membrane patches were exposed to 5 μM GABA at control (7.3), acidic (6.4), or alkaline (8.4) pH. GABA activated main and subconductance states of 24 and 16 pS, respectively, in α3β2γ2 receptors. Alkaline pHo increased channel opening frequency and decreased the duration of the long closed state, resulting in an increase in open probability (from 0.0801 ± 0.015 in pH 7.3 to 0.138 ± 0.02 in pH 8.4). Exposure of the channels to acidic pHo had the opposite effects on open probability (decreased to 0.006 ± 0.0001). Taken together, our results indicate that the function of GABAA receptors is modulated by extracellular pH. The proton effect is similar in recombinant and native receptors and is dependent on GABA concentration. In addition, the effect appears to be independent of the α-subunit isoform, and is due to the ability of H+ to alter the frequency of channel opening. Our findings indicate that GABAergic signaling in the CNS may be significantly altered during conditions that increase or decrease pH.

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Zeilhofer, H. U., D. Swandulla, P. W. Reeh e M. Kress. "Ca2+ permeability of the sustained proton-induced cation current in adult rat dorsal root ganglion neurons". Journal of Neurophysiology 76, n. 5 (1 novembre 1996): 2834–40. http://dx.doi.org/10.1152/jn.1996.76.5.2834.

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1. Microfluorometric Ca2+ measurements using FURA-2 and whole cell patch-clamp recordings were performed to investigate the Ca2+ permeability of ion channels underlying the proton-induced sustained cation current in adult rat dorsal root ganglion neurons. 2. In a subpopulation of these neurons, extracellular application of acidic solutions (pH 5.1) elicited a sustained cation current and a concomitant reversible rise in the intracellular free Ca2+ concentration ([Ca2+]i), which depended on the presence of external Ca2+. Ruthenium red (10 microM) reduced both the current and the rise in [Ca2+]i to about the same extent. 3. In the presence of 2 mM external Ca2+, sustained proton-induced currents reversed sign at -4.6 +/- 1.2 (SE) mV, with external Na+ and internal Cs+ as the major charge carriers. Increasing the external Ca2+ concentration to 30 mM shifted the reversal potential (Erev) by 3.0 +/- 0.9 mV toward more positive values, suggesting a permeability ratio of Ca2+/Cs+ of 0.41. A similar value (0.35) could be obtained from Erev (-21 mV) under bi-ionic conditions with 100 mM external Ca2+ and 154 mM internal Cs+. 4. These results demonstrate that the proton-activated cation channels investigated here are moderately permeable to Ca2+. This may lead to pathophysiologically relevant increases in [Ca2+]i on prolonged exposure of the cells to an acidic environment in inflamed or ischemic tissue.

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Lo, Stanley M., Kyle A. McElroy e Nicole J. Francis. "Chromatin Modification by PSC Occurs at One PSC per Nucleosome and Does Not Require the Acidic Patch of Histone H2A". PLoS ONE 7, n. 10 (11 ottobre 2012): e47162. http://dx.doi.org/10.1371/journal.pone.0047162.

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McNitt, Dudley H., Soo Jeon Choi, Douglas R. Keene, Livingston Van De Water, Flavia Squeglia, Rita Berisio e Slawomir Lukomski. "Surface-exposed loops and an acidic patch in the Scl1 protein of group AStreptococcusenable Scl1 binding to wound-associated fibronectin". Journal of Biological Chemistry 293, n. 20 (2 aprile 2018): 7796–810. http://dx.doi.org/10.1074/jbc.ra118.002250.

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Ye, Youpi, Hao Wu, Kangjing Chen, Cedric R. Clapier, Naveen Verma, Wenhao Zhang, Haiteng Deng, Bradley R. Cairns, Ning Gao e Zhucheng Chen. "Structure of the RSC complex bound to the nucleosome". Science 366, n. 6467 (31 ottobre 2019): 838–43. http://dx.doi.org/10.1126/science.aay0033.

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The RSC complex remodels chromatin structure and regulates gene transcription. We used cryo–electron microscopy to determine the structure of yeast RSC bound to the nucleosome. RSC is delineated into the adenosine triphosphatase motor, the actin-related protein module, and the substrate recruitment module (SRM). RSC binds the nucleosome mainly through the motor, with the auxiliary subunit Sfh1 engaging the H2A-H2B acidic patch to enable nucleosome ejection. SRM is organized into three substrate-binding lobes poised to bind their respective nucleosomal epitopes. The relative orientations of the SRM and the motor on the nucleosome explain the directionality of DNA translocation and promoter nucleosome repositioning by RSC. Our findings shed light on RSC assembly and functionality, and they provide a framework to understand the mammalian homologs BAF/PBAF and the Sfh1 ortholog INI1/BAF47, which are frequently mutated in cancers.

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