Mapping the electrostatic potential of the nucleosome acidic patch

Abstract The nucleosome surface contains an area with negative electrostatic potential known as the acidic patch, which functions as a binding platform for various proteins to regulate chromatin biology. The dense clustering of acidic residues may impact their effective pKa and thus the electronegat...

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Autores principales:	Heyi Zhang, Jelmer Eerland, Velten Horn, Raymond Schellevis, Hugo van Ingen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/544c1de6121f412da6043bec52db0a82
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spelling	oai:doaj.org-article:544c1de6121f412da6043bec52db0a822021-11-28T12:17:40ZMapping the electrostatic potential of the nucleosome acidic patch10.1038/s41598-021-02436-32045-2322https://doaj.org/article/544c1de6121f412da6043bec52db0a822021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02436-3https://doaj.org/toc/2045-2322Abstract The nucleosome surface contains an area with negative electrostatic potential known as the acidic patch, which functions as a binding platform for various proteins to regulate chromatin biology. The dense clustering of acidic residues may impact their effective pKa and thus the electronegativity of the acidic patch, which in turn could influence nucleosome-protein interactions. We here set out to determine the pKa values of residues in and around the acidic patch in the free H2A-H2B dimer using NMR spectroscopy. We present a refined solution structure of the H2A-H2B dimer based on intermolecular distance restraints, displaying a well-defined histone-fold core. We show that the conserved histidines H2B H46 and H106 that line the acidic patch have pKa of 5.9 and 6.5, respectively, and that most acidic patch carboxyl groups have pKa values well below 5.0. For H2A D89 we find strong evidence for an elevated pKa of 5.3. Our data establish that the acidic patch is highly negatively charged at physiological pH, while protonation of H2B H106 and H2B H46 at slightly acidic pH will reduce electronegativity. These results will be valuable to understand the impact of pH changes on nucleosome-protein interactions in vitro, in silico or in vivo.Heyi ZhangJelmer EerlandVelten HornRaymond SchellevisHugo van IngenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heyi Zhang Jelmer Eerland Velten Horn Raymond Schellevis Hugo van Ingen Mapping the electrostatic potential of the nucleosome acidic patch
description	Abstract The nucleosome surface contains an area with negative electrostatic potential known as the acidic patch, which functions as a binding platform for various proteins to regulate chromatin biology. The dense clustering of acidic residues may impact their effective pKa and thus the electronegativity of the acidic patch, which in turn could influence nucleosome-protein interactions. We here set out to determine the pKa values of residues in and around the acidic patch in the free H2A-H2B dimer using NMR spectroscopy. We present a refined solution structure of the H2A-H2B dimer based on intermolecular distance restraints, displaying a well-defined histone-fold core. We show that the conserved histidines H2B H46 and H106 that line the acidic patch have pKa of 5.9 and 6.5, respectively, and that most acidic patch carboxyl groups have pKa values well below 5.0. For H2A D89 we find strong evidence for an elevated pKa of 5.3. Our data establish that the acidic patch is highly negatively charged at physiological pH, while protonation of H2B H106 and H2B H46 at slightly acidic pH will reduce electronegativity. These results will be valuable to understand the impact of pH changes on nucleosome-protein interactions in vitro, in silico or in vivo.
format	article
author	Heyi Zhang Jelmer Eerland Velten Horn Raymond Schellevis Hugo van Ingen
author_facet	Heyi Zhang Jelmer Eerland Velten Horn Raymond Schellevis Hugo van Ingen
author_sort	Heyi Zhang
title	Mapping the electrostatic potential of the nucleosome acidic patch
title_short	Mapping the electrostatic potential of the nucleosome acidic patch
title_full	Mapping the electrostatic potential of the nucleosome acidic patch
title_fullStr	Mapping the electrostatic potential of the nucleosome acidic patch
title_full_unstemmed	Mapping the electrostatic potential of the nucleosome acidic patch
title_sort	mapping the electrostatic potential of the nucleosome acidic patch
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/544c1de6121f412da6043bec52db0a82
work_keys_str_mv	AT heyizhang mappingtheelectrostaticpotentialofthenucleosomeacidicpatch AT jelmereerland mappingtheelectrostaticpotentialofthenucleosomeacidicpatch AT veltenhorn mappingtheelectrostaticpotentialofthenucleosomeacidicpatch AT raymondschellevis mappingtheelectrostaticpotentialofthenucleosomeacidicpatch AT hugovaningen mappingtheelectrostaticpotentialofthenucleosomeacidicpatch
_version_	1718408076673941504

Mapping the electrostatic potential of the nucleosome acidic patch

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