Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 283, Issue 52, Pages 36532-36541Publisher
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DOI: 10.1074/jbc.M807144200
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Funding
- Intramural [MLP007]
- Council of Scientific and Industrial Research, India [CMM0017]
- Central Drug Research Institute
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Rv3868, a conserved hypothetical protein of the ESAT-6 secretion system of Mycobacterium tuberculosis, is essential for the secretion of at least four virulence factors. Each protein chain is similar to 63 kDa and assembles into a hexamer. Limited proteolysis demonstrates that it consists of two domains joined by a linker. The N-terminal domain is a compact, helical domain of similar to 30 kDa and apparently functions to regulate the ATPase activity of the C-terminal domain and the oligomerization. The nucleotide binding site is situated in the C-terminal domain, which exhibits ATP-dependent self-association. It is also the oligomerization domain. Dynamic fluorescence quenching studies demonstrate that the domain is proximal to the C terminus in the apoprotein and exhibits a specific movement upon ATP binding. In silico modeling of the domains suggests that Arg-429 of a neighboring subunit forms a part of the binding site upon oligomerization. Mutational analysis of binding site residues demonstrates that the Arg-429 functions as the important sensor arginine in AAA-ATPases. Protein NMR experiments involving CFP-10 and activity assays rule out a general chaperone-like function for Rv3868. On the other hand, ATP-dependent open-close movements of the individual domains apparently enable it to interact and transfer energy to co-proteins in the ESX-1 pathway.
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