Identification of lysine methylation in the core GTPase domain by GoMADScan

PloS One
Hirofumi YoshinoAtsuo T Sasaki

Abstract

RAS is the founding member of a superfamily of GTPases and regulates signaling pathways involved in cellular growth control. While recent studies have shown that the activation state of RAS can be controlled by lysine ubiquitylation and acetylation, the existence of lysine methylation of the RAS superfamily GTPases remains unexplored. In contrast to acetylation, methylation does not alter the side chain charge and it has been challenging to deduce its impact on protein structure by conventional amino acid substitutions. Herein, we investigate lysine methylation on RAS and RAS-related GTPases. We developed GoMADScan (Go language-based Modification Associated Database Scanner), a new user-friendly application that scans and extracts posttranslationally modified peptides from databases. The GoMADScan search on PhosphoSitePlus databases identified methylation of conserved lysine residues in the core GTPase domain of RAS superfamily GTPases, including residues corresponding to RAS Lys-5, Lys-16, and Lys-117. To follow up on these observations, we immunoprecipitated endogenous RAS from HEK293T cells, conducted mass spectrometric analysis and found that RAS residues, Lys-5 and Lys-147, undergo dimethylation and monomethylation, respec...Continue Reading

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Citations

Jul 27, 2021·Frontiers in Molecular Biosciences·Natsuki OsakaAtsuo T Sasaki

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Methods Mentioned

BETA
GTPase
nucleotide
GTPases
acetylation
pull-down

Clinical Trials Mentioned

NCT03600883
NCT03785249

Software Mentioned

tleap
GTK
Proteomics Browser
PhosphoSitePlus
OS X
Go
PMEMD
Amber16
ff14SB
GraphMod

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