Revealing a Hidden Intermediate of Rotatory Catalysis with X-ray Crystallography and Molecular Simulations.

ABSTRACT: The mechanism of rotatory catalysis in ATP-hydrolyzing molecular motors remains an unresolved puzzle in biological energy transfer. Notwithstanding the wealth of available biochemical and structural information inferred from years of experiments, knowledge on how the coupling between the chemical and mechanical steps within motors enforces directional rotatory movements remains fragmentary. Even more contentious is to pinpoint the rate-limiting step of a multistep rotation process. Here, using vacuolar or V₁-type hexameric ATPase as an exemplary rotational motor, we present a model of the complete 4-step conformational cycle involved in rotatory catalysis. First, using X-ray crystallography, a new intermediate or "dwell" is identified, which enables the release of an inorganic p

SUBMITTER: Shekhar M 

PROVIDER: S-EPMC9336149 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature