Crystal structure of A sub(3)B sub(3) complex of V-ATPase from Thermus thermophilus

• Published in: The EMBO journal Vol. 28; no. 23; pp. 3771 - 3779
• Main Authors: Maher, Megan J, Akimoto, Satoru, Iwata, Momi, Nagata, Koji, Hori, Yoshiko, Yoshida, Masasuke, Yokoyama, Shigeyuki, Iwata, So, Yokoyama, Ken
• Format: Journal Article
• Language: English
• Published: 02.12.2009
• Subjects: Thermus thermophilus
• ISSN: 0261-4189
• DOI: 10.1038/emboj.2009.310

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 sub(3)B sub(3) subcomplex of V-ATPase at 2.8 Aa resolution. The overall construction of the A sub(3)B sub(3) subcomplex is significantly different from that of the a sub(3)b sub(3) sub-domain in F sub(o)F sub(1)-ATP synthase, because of the presence of a protruding 'bulge' domain feature in the catalytic A subunits. The A sub(3)B sub(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 F sub(o)F sub(1)-ATP synthase. In the catalytic interface, our mutational analysis, on the basis of the A sub(3)B sub(3) structure, has highlighted the presence of a cluster composed of key hydrophobic residues, which are essential for ATP hydrolysis by V-ATPases.