结核分枝杆菌的核苷二磷酸激酶作为Rho-GTP酶的GTP酶激活蛋白。

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

作者信息

Chopra Puneet, Koduri Harshavardhan, Singh Ramandeep, Koul Anil, Ghildiyal Megha, Sharma Kirti, Tyagi Anil K, Singh Yogendra

机构信息

Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.

出版信息

FEBS Lett. 2004 Jul 30;571(1-3):212-6. doi: 10.1016/j.febslet.2004.06.073.

DOI:10.1016/j.febslet.2004.06.073

PMID:15280044

Abstract

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.

摘要

几种细菌病原体将蛋白质分泌到宿主细胞中，这些蛋白质作为Rho-GTPases的GTP酶激活蛋白（GAPs），将结合GTP的活性形式转化为结合GDP的无活性形式。然而，在结核分枝杆菌中尚未鉴定出此类效应分子。在本研究中，我们表明结核分枝杆菌H(37)Rv的培养上清液中含有一种蛋白质，该蛋白质可刺激结合GTP的Rho-GTPases转化为结合GDP的形式。核苷二磷酸激酶（Ndk）被鉴定为这种培养上清液蛋白，它可刺激Rho-GTPases成员在体外进行GTP水解。Ndk的组氨酸-117突变体，其自身磷酸化和核苷酸结合活性受损，但仍具有GAP活性。这些结果表明，结核分枝杆菌的Ndk作为一种Rho-GAP发挥作用，下调Rho-GTPases，并且这种活性可能有助于细菌的致病过程。