Mechanism of actin N-terminal acetylation.
Acetylation
Acetyltransferases
/ chemistry
Actins
/ chemistry
Amino Acid Sequence
Binding Sites
Fluorescent Antibody Technique
Humans
Models, Molecular
Molecular Conformation
Profilins
/ metabolism
Protein Binding
Protein Domains
Protein Isoforms
/ metabolism
Protein Multimerization
Structure-Activity Relationship
Substrate Specificity
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
25
07
2019
accepted:
14
01
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
16
12
2020
Statut:
epublish
Résumé
About 80% of human proteins are amino-terminally acetylated (Nt-acetylated) by one of seven Nt-acetyltransferases (NATs). Actin, the most abundant protein in the cytoplasm, has its own dedicated NAT, NAA80, which acts posttranslationally and affects cytoskeleton assembly and cell motility. Here, we show that NAA80 does not associate with filamentous actin in cells, and its natural substrate is the monomeric actin-profilin complex, consistent with Nt-acetylation preceding polymerization. NAA80 Nt-acetylates actin-profilin much more efficiently than actin alone, suggesting that profilin acts as a chaperone for actin Nt-acetylation. We determined crystal structures of the NAA80-actin-profilin ternary complex, representing different actin isoforms and different states of the catalytic reaction and revealing the first structure of NAT-substrate complex at atomic resolution. The structural, biochemical, and cellular analysis of mutants shows how NAA80 has evolved to specifically recognize actin among all cellular proteins while targeting all six actin isoforms, which differ the most at the amino terminus.
Identifiants
pubmed: 32284999
doi: 10.1126/sciadv.aay8793
pii: aay8793
pmc: PMC7141826
doi:
Substances chimiques
Actins
0
Profilins
0
Protein Isoforms
0
Acetyltransferases
EC 2.3.1.-
NAA80 protein, human
EC 2.3.1.-
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
eaay8793Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM073791
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH087950
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Références
Trends Biochem Sci. 2016 Sep;41(9):746-760
pubmed: 27498224
Methods. 2011 Sep;55(1):94-106
pubmed: 21821126
Biochemistry. 1998 Aug 4;37(31):10871-80
pubmed: 9692980
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4405-4410
pubmed: 29581307
FEBS J. 2018 Sep;285(17):3299-3316
pubmed: 30028079
Cytoskeleton (Hoboken). 2018 Jul;75(7):318-322
pubmed: 30084538
Trends Biochem Sci. 2019 Jun;44(6):502-516
pubmed: 30611609
Methods Mol Biol. 2014;1079:263-71
pubmed: 24170408
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404
pubmed: 29581253
Handb Exp Pharmacol. 2017;235:331-347
pubmed: 27873086
Science. 2015 Mar 13;347(6227):1249-1252
pubmed: 25766235
Methods Mol Biol. 2017;1574:1-8
pubmed: 28315239
Nat Protoc. 2015 Jun;10(6):845-58
pubmed: 25950237
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8157-62
pubmed: 19420222
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4265-4274
pubmed: 30760599
Biochemistry. 1996 Dec 24;35(51):16535-43
pubmed: 8987987
Methods Enzymol. 1982;85 Pt B:164-81
pubmed: 7121269
Compr Physiol. 2016 Mar 15;6(2):1043-69
pubmed: 27065174
Curr Biol. 2018 Jul 23;28(14):2331-2337.e5
pubmed: 29983319
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4314-4316
pubmed: 29632202
J Appl Physiol (1985). 2000 Mar;88(3):1127-32
pubmed: 10710412
Biophys J. 2011 Feb 16;100(4):797-8
pubmed: 21320421
Annu Rev Biophys. 2011;40:169-86
pubmed: 21314430
EMBO J. 2007 Oct 31;26(21):4597-606
pubmed: 17914456
PLoS One. 2011;6(9):e24713
pubmed: 21935442
Science. 1999 Dec 3;286(5446):1939-42
pubmed: 10583954
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Proteins. 2002 Aug 1;48(2):227-41
pubmed: 12112692
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Trends Biochem Sci. 2016 Jun;41(6):478-490
pubmed: 27068179
Exp Cell Res. 1976 Feb;97(2):387-93
pubmed: 1248526
Cell Rep. 2015 Mar 3;10(8):1362-74
pubmed: 25732826
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4596-605
pubmed: 25313062
Mol Cell. 2019 Mar 21;73(6):1097-1114
pubmed: 30878283
Int Rev Cytol. 2001;202:35-98
pubmed: 11061563
Electrophoresis. 2009 Mar;30(5):848-51
pubmed: 19197901