title: Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli.
abstract: Lysine succinylation is a newly identified protein post-translational modification pathway present in both prokaryotic and eukaryotic cells. However, succinylation substrates and regulatory enzyme(s) remain largely unknown, hindering the biological study of this modification. Here we report the identification of 2,580 bacterial lysine succinylation sites in 670 proteins and 2,803 lysine acetylation (Kac) sites in 782 proteins, representing the first lysine succinylation dataset and the largest Kac dataset in wild-type E. coli. We quantified dynamic changes of the lysine succinylation and Kac substrates in response to high glucose. Our data showed that high-glucose conditions led to more lysine-succinylated proteins and enhanced the abundance of succinyllysine peptides more significantly than Kac peptides, suggesting that glucose has a more profound effect on succinylation than on acetylation. We further identified CobB, a known Sir2-like bacterial lysine deacetylase, as the first prokaryotic desuccinylation enzyme. The identification of bacterial CobB as a bifunctional enzyme with lysine desuccinylation and deacetylation activities suggests that the eukaryotic Kac-regulatory enzymes may have enzymatic activities on various lysine acylations with very different structures. In addition, it is highly likely that lysine succinylation could have unique and more profound regulatory roles in cellular metabolism relative to lysine acetylation under some physiological conditions.
authors.affiliation: Ben May Department of Cancer Research, University of Chicago, Chicago, Illinois 60637;
authors.forename: Gozde
authors.initials: G
authors.lastname: Colak
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Xie
authors.forename: Anita Y
authors.initials: AY
authors.lastname: Zhu
authors.forename: Lunzhi
authors.initials: L
authors.lastname: Dai
authors.forename: Zhike
authors.initials: Z
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wan
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Yoon H
authors.initials: YH
authors.lastname: Cha
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
mesh_terms: D000107:Acetylation; D000214:Acyl Coenzyme A / Q000378:metabolism*; D020816:Amino Acid Motifs; D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007553:Isotope Labeling; D008239:Lysine / Q000378:metabolism; D058977:Molecular Sequence Annotation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D000214:Acyl Coenzyme A; D029968:Escherichia coli Proteins; C012046:succinyl-coenzyme A; D037761:Sirtuins; C483998:cobB protein, E Coli; D005947:Glucose; D008239:Lysine