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Mol Cell Proteomics. 2017 Aug;16(8):1491-1506. doi: 10.1074/mcp.M116.065771. Epub 2017 Jun 1.

The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

Wu FL1,2, Liu Y1,2, Jiang HW1,2, Luan YZ3, Zhang HN1,2, He X1,2,4, Xu ZW1,2, Hou JL5, Ji LY1, Xie Z3, Czajkowsky DM4, Yan W1, Deng JY6, Bi LJ7,8,9, Zhang XE7, Tao SC10,2,4.

Author information

1
From the ‡Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
2
§State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China.
3
¶State Key Lab of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou 500040, China.
4
‖School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
5
**Instrumental Analysis Center of Shanghai Jiao Tong University, Shanghai 200240, China.
6
‡‡State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
7
§§National Key Laboratory of Biomacromolecules, Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
8
¶¶School of Stomatology and Medicine, Foshan University, Foshan 528000, Guangdong Province, China.
9
‖‖Guangdong Province Key Laboratory of TB Systems Biology and Translational Medicine, Foshan 528000, China.
10
From the ‡Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; taosc@sjtu.edu.cn.

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb.

PMID:
28572091
PMCID:
PMC5546200
DOI:
10.1074/mcp.M116.065771
[Indexed for MEDLINE]
Free PMC Article

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