Crystal structure of A3B3 complex of V-ATPase from Thermus thermophilus

Vacuolar-type ATPases (V-ATPases) exist in various cellular membranes of many organisms to regulate physiological processes by controlling the acidic environment. Here, we have determined the crystal structure of the A(3)B(3) subcomplex of V-ATPase at 2.8 angstrom resolution. The overall construction of the A(3)B(3) subcomplex is significantly different from that of the alpha(3)beta(3) sub-domain in FoF1-ATP synthase, because of the presence of a protruding 'bulge' domain feature in the catalytic A subunits. The A(3)B(3) subcomplex structure provides the first molecular insight at the catalytic and non-catalytic interfaces, which was not possible in the structures of the separate subunits alone. Specifically, in the non-catalytic interface, the B subunit seems to be incapable of binding ATP, which is a marked difference from the situation indicated by the structure of the FoF1-ATP synthase. In the catalytic interface, our mutational analysis, on the basis of the A(3)B(3) structure, has highlighted the presence of a cluster composed of key hydrophobic residues, which are essential for ATP hydrolysis by V-ATPases. The EMBO Journal (2009) 28, 3771-3779. doi: 10.1038/emboj.2009.310; Published online 5 November 2009