Mechanical inhibition of isolated V o from V/A-ATPase for proton conductance.

V-ATPase is an energy converting enzyme, coupling ATP hydrolysis/synthesis in the hydrophilic V ₁ domain, with proton flow through the V _o membrane domain, via rotation of the central rotor complex relative to the surrounding stator apparatus. Upon dissociation from the V ₁ domain, the V _o domain of the eukaryotic V-ATPase can adopt a physiologically relevant auto-inhibited form in which proton conductance through the V _o domain is prevented, however the molecular mechanism of this inhibition is not fully understood. Using cryo-electron microscopy, we determined the structure of both the holo V/A-ATPase and isolated V _o at near-atomic resolution, respectively. These structures clarify how the isolated V _o domain adopts the auto-inhibited form and how the holo complex prevents formation of the inhibited V _o form.
Competing Interests: JK, AN, AF, TK, KN, MT, KM, KY No competing interests declared
(© 2020, Kishikawa et al.)