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Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications
Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less k...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAAS
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076270/ https://www.ncbi.nlm.nih.gov/pubmed/37040526 http://dx.doi.org/10.34133/research.0109 |
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author | Li, Sha Li, Nan He, Jie Zhou, Runxin Lu, Zhimin Tao, Yizhi Jane Guo, Yusong R. Wang, Yugang |
author_facet | Li, Sha Li, Nan He, Jie Zhou, Runxin Lu, Zhimin Tao, Yizhi Jane Guo, Yusong R. Wang, Yugang |
author_sort | Li, Sha |
collection | PubMed |
description | Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells. |
format | Online Article Text |
id | pubmed-10076270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AAAS |
record_format | MEDLINE/PubMed |
spelling | pubmed-100762702023-04-07 Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications Li, Sha Li, Nan He, Jie Zhou, Runxin Lu, Zhimin Tao, Yizhi Jane Guo, Yusong R. Wang, Yugang Research (Wash D C) Rapid Report Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells. AAAS 2023-04-04 /pmc/articles/PMC10076270/ /pubmed/37040526 http://dx.doi.org/10.34133/research.0109 Text en Copyright © 2023 Sha Li et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Rapid Report Li, Sha Li, Nan He, Jie Zhou, Runxin Lu, Zhimin Tao, Yizhi Jane Guo, Yusong R. Wang, Yugang Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title | Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title_full | Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title_fullStr | Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title_full_unstemmed | Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title_short | Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications |
title_sort | molecular basis of kat2a selecting acyl-coa cofactors for histone modifications |
topic | Rapid Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076270/ https://www.ncbi.nlm.nih.gov/pubmed/37040526 http://dx.doi.org/10.34133/research.0109 |
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