Methionine to isothreonine conversion as a source of false discovery identifications of genetically encoded variants in proteogenomics

Journal of Proteomics
Alexey L ChernobrovkinSergei A Moshkovskii

Abstract

Searching deep proteome data for 9 NCI-60 cancer cell lines obtained earlier by Moghaddas Gholami et al. (Cell Reports, 2013) against a database from cancer genomes returned a variant tryptic peptide fragment 57-72 of molecular chaperone HSC70, in which methionine residue at 61 position is replaced by threonine, or isothreonine (homoserine), residue. However, no traces of the corresponding genetic alteration were found in the cell line genomes reported by Abaan et al. (Cancer Research, 2013). Studying on the background of this modification led us to conclude that a conversion of methionine into isothreonine resulted from iodoacetamide treatment of the probe during a sample preparation step. We found that up to 10% of methionine containing peptides experienced the above conversion for the datasets under study. The artifact was confirmed by model experiment with bovine albumin, where three of four methionine residues were partly converted to isothreonine by conventional iodoacetamide treatment. This experimental side reaction has to be taken into account when searching for genetically encoded peptide variants in the proteogenomics studies. A lot of effort is currently put into proteogenomics of cancer. Studies detect non-synonymo...Continue Reading

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Citations

Jul 16, 2015·Expert Review of Proteomics·Anna PolyakovaSergei Moshkovskii
May 14, 2016·Rapid Communications in Mass Spectrometry : RCM·Ksenia G KuznetsovaSergei A Moshkovskii
Apr 7, 2016·Annual Review of Analytical Chemistry·Gloria M SheynkmanLloyd M Smith
Nov 11, 2017·Bulletin of Experimental Biology and Medicine·V Kh KhavinsonN S Lin'kova
Jan 5, 2018·Journal of the American Society for Mass Spectrometry·Mark V IvanovMikhail V Gorshkov
Nov 1, 2016·Biomedit︠s︡inskai︠a︡ khimii︠a︡·A A KliuchnikovaS A Moshkovskii
Oct 3, 2019·Proteomics·Lev I LevitskySergei A Moshkovskii
Feb 6, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Lampros DimitrakopoulosGeorge S Charames
Mar 3, 2020·Biomedit︠s︡inskai︠a︡ khimii︠a︡·K G KuznetsovaS A Moshkovskii
Apr 8, 2018·Biochemistry. Biokhimii︠a︡·S A MoshkovskiiM V Gorshkov
Mar 31, 2019·Biochemistry. Biokhimii︠a︡·K G KuznetsovaS A Moshkovskii
Oct 24, 2020·Journal of Proteomics·Ksenia G KuznetsovaSergei A Moshkovskii
Oct 10, 2018·Journal of Proteome Research·Ksenia G KuznetsovaSergei A Moshkovskii
May 3, 2019·Analytical Chemistry·Elizaveta M SolovyevaOleg V Boyarkin
Nov 2, 2021·Mass Spectrometry Reviews·Tai-Tu LinTujin Shi

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