Proximal Cysteines that Enhance Lysine N-Acetylation of Cytosolic Proteins in Mice Are Less Conserved in Longer-Living Species.

TitleProximal Cysteines that Enhance Lysine N-Acetylation of Cytosolic Proteins in Mice Are Less Conserved in Longer-Living Species.
Publication TypeJournal Article
Year of Publication2018
AuthorsJames, AM, Smith, AC, Smith, CL, Robinson, AJ, Murphy, MP
JournalCell Rep
Volume24
Issue6
Pagination1445-1455
Date Published2018 Aug 07
ISSN2211-1247
Abstract

Acetyl-coenzyme A (CoA) is an abundant metabolite that can also alter protein function through non-enzymatic N-acetylation of protein lysines. This N-acetylation is greatly enhanced in vitro if an adjacent cysteine undergoes initial S-acetylation, as this can lead to S→N transfer of the acetyl moiety. Here, using modeled mouse structures of 619 proteins N-acetylated in mouse liver, we show lysine N-acetylation is greater in vivo if a cysteine is within ∼10 Å. Extension to the genomes of 52 other mammalian and bird species shows pairs of proximal cysteine and N-acetylated lysines are less conserved, implying most N-acetylation is detrimental. Supporting this, there is less conservation of cytosolic pairs of proximal cysteine and N-acetylated lysines in species with longer lifespans. As acetyl-CoA levels are linked to nutrient supply, these findings suggest how dietary restriction could extend lifespan and how pathologies resulting from dietary excess may occur.

DOI10.1016/j.celrep.2018.07.007
Alternate JournalCell Rep
Citation Key10.1016/j.celrep.2018.07.007
PubMed ID30089256
PubMed Central IDPMC6092265
Grant List / / Wellcome Trust / United Kingdom
MC_U105663142 / / Medical Research Council / United Kingdom
MC_U105674181 / / Medical Research Council / United Kingdom