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Proteomics. 2018 Dec;18(23):e1800265. doi: 10.1002/pmic.201800265. Epub 2018 Oct 24.

Global Profiling of PknG Interactions Using a Human Proteome Microarray Reveals Novel Connections with CypA.

Wu FL1,2,3, Liu Y1,2, Zhang HN1,2, Jiang HW1,2, Cheng L1,2, Guo SJ1,2, Deng JY4, Bi LJ5,6,7,8, Zhang XE5, Gao HF9, Tao SC1,2.

Author information

1
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 200240, Shanghai, P. R. China.
2
School of Biomedical Engineering, Shanghai Jiao Tong University, 200240, Shanghai, P. R. China.
3
School of Agriculture, Ludong University, Yantai, 264025, P. R. China.
4
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, P. R. China.
5
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, 100101, Beijing, P. R. China.
6
School of Stomatology and Medicine, Foshan University, Foshan, 528000, Guangdong Province, P. R. China.
7
TB Healthcare Biotechnology Co., Ltd., Foshan, 528000, Guangdong Province, P. R. China.
8
Guangdong Province Key Laboratory of TB Systems Biology and Translational Medicine, Foshan, 528000, Guangdong Province, P. R. China.
9
National Research Institute for Health and Family Planning, 100081, Beijing, P. R. China.

Abstract

Mycobacterium tuberculosis (Mtb) serine/threonine kinase PknG plays an important role in the Mtb-host interaction by facilitating the survival of Mtb in macrophages. However, the human proteins with which the PknG interacts, and the underlying molecular mechanisms are still largely unknown. In this study, a HuProt array is been applied to globally identify the host proteins to which PknG binds. In this way, 125 interactors are discovered, including a cyclophilin protein, CypA. This interaction between PknG and CypA is validated both in vitro and in vivo, and functional studies show that PknG significantly reduces the protein levels of CypA through phosphorylation, which consequently inhibit the inflammatory response through downregulation of NF-κB and ERK1/2 pathways. Phenotypically, overexpression of PknG reduces cytokine levels and promotes the survival of Mycobacterium smegmatis (Msm) in macrophages. Overall, it is expected that the PknG interactors identified in this study will serve as a useful resource for further systematic studies of the roles that PknG plays in the Mtb-host interactions.

KEYWORDS:

CypA; ERK1/2; HuProt array; NF-κB; PknG

PMID:
30281201
DOI:
10.1002/pmic.201800265

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