Nucleoside diphosphate kinase of Mycobacterium tuberculosis acts as GTPase-activating protein for Rho-GTPases

被引:27
作者
Chopra, P
Koduri, H
Singh, R
Koul, A
Ghildiyal, M
Sharma, K
Tyagi, AK
Singh, Y
机构
[1] Inst Genom & Integrat Biol, Delhi, India
[2] Univ Delhi, Dept Biochem, New Delhi, India
[3] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, New Delhi, India
关键词
nucleoside diphosphate kinase; tuberculosis; G-protein; GTPase activating protein; actin cytoskeleton; Mycobacterium;
D O I
10.1016/j.febslet.2004.06.073
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several bacterial pathogens secrete proteins into the host cells that act as GTPase-activating proteins (GAPs) for Rho-GTPases and convert GTP-bound active form to GDP-bound inactive form. However, no such effector molecule has been identified in Mycobacterium tuberculosis. In this study, we show that culture supernatant of M. tuberculosis H(37)Rv harbors a protein that stimulates the conversion of GTP-bound Rho-GTPases to the GDP-bound form. Nucleoside diphosphate kinase (Ndk) was identified as this culture supernatant protein that stimulated in vitro GTP hydrolysis by members of Rho-GTPases. The histidine-117 mutant of Ndk, which is impaired for autophosphorylation and nucleotide-binding activities, shows GAP activity. These results suggest that Ndk of M. tuberculosis functions as a Rho-GAP to downregulate Rho-GTPases, and this activity may aid in pathogenesis of the bacteria. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:212 / 216
页数:5
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