Proximal cysteines enhance lysine acetylation of cytosolic proteins and are selected against in long-lived species
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Murphy, M. Proximal cysteines enhance lysine acetylation of cytosolic proteins and are selected against in long-lived species. Cell Reports https://doi.org/10.17863/CAM.27391
Acetyl-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 modelled mouse structures of 619 proteins N-acetylated in mouse liver, we show lysine N-acetylation is greater in vivo if a cysteine is within ~10Å. 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 was 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.
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
This record's DOI: https://doi.org/10.17863/CAM.27391
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280027