Nucleoside diphosphate kinase of Mycobacterium tuberculosis acts as GTPase-activating protein for Rho-GTPases.
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.
Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
Puneet
P
Chopra
Harshavardhan
H
Koduri
Ramandeep
R
Singh
Anil
A
Koul
Megha
M
Ghildiyal
Kirti
K
Sharma
Anil K
AK
Tyagi
Yogendra
Y
Singh
D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D009701:Nucleoside-Diphosphate Kinase; D020558:GTP Phosphohydrolases