title: Identification of lysine succinylation as a new post-translational modification.
abstract: Of the 20 ribosomally coded amino acid residues, lysine is the most frequently post-translationally modified, which has important functional and regulatory consequences. Here we report the identification and verification of a previously unreported form of protein post-translational modification (PTM): lysine succinylation. The succinyllysine residue was initially identified by mass spectrometry and protein sequence alignment. The identified succinyllysine peptides derived from in vivo proteins were verified by western blot analysis, in vivo labeling with isotopic succinate, MS/MS and HPLC coelution of their synthetic counterparts. We further show that lysine succinylation is evolutionarily conserved and that this PTM responds to different physiological conditions. Our study also implies that succinyl-CoA might be a cofactor for lysine succinylation. Given the apparent high abundance of lysine succinylation and the significant structural changes induced by this PTM, it is expected that lysine succinylation has important cellular functions.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Xie
authors.forename: Lunzhi
authors.initials: L
authors.lastname: Dai
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D019802:Succinic Acid / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D029968:Escherichia coli Proteins; D010455:Peptides; D019802:Succinic Acid; C012046:succinyl-coenzyme A; D008239:Lysine