Structure of the vacuolar H+-ATPase rotary motor reveals new mechanistic insights

Summary Vacuolar H+-ATPases are multisubunit complexes that operate with rotary mechanics and are essential for membrane proton transport throughout eukaryotes. Here we report a ∼1 nm resolution reconstruction of a V-ATPase in a different conformational state from that previously reported for a lower-resolution yeast model. The stator network of the V-ATPase (and by implication that of other rotary ATPases) does not change conformation in different catalytic states, and hence must be relatively rigid. We also demonstrate that a conserved bearing in the catalytic domain is electrostatic, contributing to the extraordinarily high efficiency of rotary ATPases. Analysis of the rotor axle/membrane pump interface suggests how rotary ATPases accommodate different c ring stoichiometries while maintaining high efficiency. The model provides evidence for a half channel in the proton pump, supporting theoretical models of ion translocation. Our refined model therefore provides new insights into the structure and mechanics of the V-ATPases.
Graphical Abstract
Highlights • Subnanometer V-ATPase EM structure gives new insights into mechanism • Comparison of two distinct catalytic states in a complete rotary ATPase • Describes a conserved electrostatic bearing that supports high motor efficiency • Proposes how different c ring stoichiometries are accommodated
Rawson et al. solve a high-resolution structure of vacuolar ATPase. The complex rests in a catalytic state different from those previously reported. The work gives new insights into the organization, mechanism, and the basis for functional properties such as high thermodynamic efficiency.