Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 09 2022
16 09 2022
Historique:
received:
02
11
2021
accepted:
26
08
2022
entrez:
16
9
2022
pubmed:
17
9
2022
medline:
21
9
2022
Statut:
epublish
Résumé
Covalent attachment of ubiquitin (Ub) to proteins is a highly versatile posttranslational modification. Moreover, Ub is not only a modifier but itself is modified by phosphorylation and lysine acetylation. However, the functional consequences of Ub acetylation are poorly understood. By generation and comprehensive characterization of all seven possible mono-acetylated Ub variants, we show that each acetylation site has a particular impact on Ub structure. This is reflected in selective usage of the acetylated variants by different E3 ligases and overlapping but distinct interactomes, linking different acetylated variants to different cellular pathways. Notably, not only electrostatic but also steric effects contribute to acetylation-induced changes in Ub structure and, thus, function. Finally, we provide evidence that p300 acts as a position-specific Ub acetyltransferase and HDAC6 as a general Ub deacetylase. Our findings provide intimate insights into the structural and functional consequences of Ub acetylation and highlight the general importance of Ub acetylation.
Identifiants
pubmed: 36114200
doi: 10.1038/s41467-022-33087-1
pii: 10.1038/s41467-022-33087-1
pmc: PMC9481602
doi:
Substances chimiques
Ubiquitin
0
Acetyltransferases
EC 2.3.1.-
Ubiquitin-Protein Ligases
EC 2.3.2.27
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5435Informations de copyright
© 2022. The Author(s).
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