Top-down proteomics reveals a unique protein S-thiolation switch in Salmonella Typhimurium in response to infection-like conditions

被引:134
作者
Ansong, Charles [1 ]
Wu, Si [2 ]
Meng, Da [3 ]
Liu, Xiaowen [4 ,6 ]
Brewer, Heather M. [2 ]
Kaiser, Brooke L. Deatherage [1 ]
Nakayasu, Ernesto S. [1 ]
Cort, John R. [1 ]
Pevzner, Pavel [5 ]
Smith, Richard D. [1 ]
Heffron, Fred [7 ]
Adkins, Joshua N. [1 ]
Pasa-Tolic, Ljiljana [2 ]
机构
[1] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA
[2] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA
[3] Pacific NW Natl Lab, Computat Sci & Math Div, Richland, WA 99352 USA
[4] Indiana Univ Purdue Univ, Sch Informat, Indianapolis, IN 46202 USA
[5] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA
[6] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA
[7] Oregon Hlth & Sci Univ, Dept Microbiol & Immunol, Portland, OR 97239 USA
基金
美国国家卫生研究院;
关键词
ENTERICA SEROVAR TYPHIMURIUM; GLUTATHIONYLATED PROTEINS; VIRULENCE FACTORS; ESCHERICHIA-COLI; MASS; SECRETION; DISCOVERY; CYSTEINYLATION; IDENTIFICATION; REQUIREMENTS;
D O I
10.1073/pnas.1221210110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Characterization of the mature protein complement in cells is crucial for a better understanding of cellular processes on a systems-wide scale. Toward this end, we used single-dimension ultra-high-pressure liquid chromatography mass spectrometry to investigate the comprehensive "intact" proteome of the Gram-negative bacterial pathogen Salmonella Typhimurium. Top-down proteomics analysis revealed 563 unique proteins including 1,665 proteoforms generated by posttranslational modifications (PTMs), representing the largest microbial top-down dataset reported to date. We confirmed many previously recognized aspects of Salmonella biology and bacterial PTMs, and our analysis also revealed several additional biological insights. Of particular interest was differential utilization of the protein S-thiolation forms S-glutathionylation and S-cysteinylation in response to infection-like conditions versus basal conditions. This finding of a S-glutathionylation-to-S-cysteinylation switch in a condition-specific manner was corroborated by bottom-up proteomics data and further by changes in corresponding biosynthetic pathways under infection-like conditions and during actual infection of host cells. This differential utilization highlights underlying metabolic mechanisms that modulate changes in cellular signaling, and represents a report of S-cysteinylation in Gram-negative bacteria. Additionally, the functional relevance of these PTMs was supported by protein structure and gene deletion analyses. The demonstrated utility of our simple proteome-wide intact protein level measurement strategy for gaining biological insight should promote broader adoption and applications of top-down proteomics approaches.
引用
收藏
页码:10153 / 10158
页数:6
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