Molecular role of NAA38 in thermostability and catalytic activity of the human NatC N-terminal acetyltransferase.
N-terminal acetylation
N-terminal acetyltransferase
NATs
NatC
co-translational modification
enzyme mechanism
ribosome
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
02 02 2023
02 02 2023
Historique:
received:
01
05
2022
revised:
22
11
2022
accepted:
15
12
2022
pmc-release:
02
02
2024
pubmed:
14
1
2023
medline:
8
2
2023
entrez:
13
1
2023
Statut:
ppublish
Résumé
N-terminal acetylation occurs on over 80% of human proteins and is catalyzed by a family of N-terminal acetyltransferases (NATs). All NATs contain a small catalytic subunit, while some also contain a large auxiliary subunit that facilitates catalysis and ribosome targeting for co-translational acetylation. NatC is one of the major NATs containing an NAA30 catalytic subunit, but uniquely contains two auxiliary subunits, large NAA35 and small NAA38. Here, we report the cryo-EM structures of human NatC (hNatC) complexes with and without NAA38, together with biochemical studies, to reveal that NAA38 increases the thermostability and broadens the substrate-specificity profile of NatC by ordering an N-terminal segment of NAA35 and reorienting an NAA30 N-terminal peptide binding loop for optimal catalysis, respectively. We also note important differences in engagement with a stabilizing inositol hexaphosphate molecule between human and yeast NatC. These studies provide new insights for the function and evolution of the NatC complex.
Identifiants
pubmed: 36638802
pii: S0969-2126(22)00494-4
doi: 10.1016/j.str.2022.12.008
pmc: PMC9898148
mid: NIHMS1860930
pii:
doi:
Substances chimiques
N-Terminal Acetyltransferase C
EC 2.3.1.256
NAA30 protein, human
EC 2.3.1.256
Saccharomyces cerevisiae Proteins
0
NAA38 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166-173.e4Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM133398
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118090
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM132039
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM071339
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103873
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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