Open AccessProteome‐wide identification of mycobacterial pupylation targets
Author(s) -
Poulsen Christian,
Akhter Yusuf,
Jeon Amy HyeWon,
SchmittUlms Gerold,
Meyer Helmut E,
Stefanski Anja,
Stühler Kai,
Wilmanns Matthias,
Song YoungHwa
Publication year - 2010
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2010.39
Subject(s) - biology , proteome , mycobacterium smegmatis , gene , proteomics , proteasome , genome , genetics , metabolic pathway , biochemistry , computational biology , microbiology and biotechnology , mycobacterium tuberculosis , medicine , tuberculosis , pathology
Mycobacteria use a unique system for covalently modifying proteins based on the conjugation of a small protein, referred to as prokaryotic ubiquitin‐like protein (PUP). In this study, we report a proteome‐wide analysis of endogenous pupylation targets in the model organism Mycobacterium smegmatis . On affinity capture, a total of 243 candidate pupylation targets were identified by two complementary proteomics approaches. For 41 of these protein targets, direct evidence for a total of 48 lysine‐mediated pupylation acceptor sites was obtained by collision‐induced dissociation spectra. For the majority of these pupylation targets (38 of 41), orthologous genes are found in the M. tuberculosis genome. Interestingly, approximately half of these proteins are involved in intermediary metabolism and respiration pathways. A considerable fraction of the remaining targets are involved in lipid metabolism, information pathways, and virulence, detoxification and adaptation. Approximately one‐third of the genes encoding these targets are located in seven gene clusters, indicating functional linkages of mycobacterial pupylation targets. A comparison of the pupylome under different cell culture conditions indicates that substrate targeting for pupylation is rather dynamic.