How Does F-ATPase Generate Torque?: Analysis From Cryo-Electron Microscopy and Rotational Catalysis of Thermophilic F

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2022 May 23

PMID 35602057

Authors

Hiroyuki Noji

Hiroshi Ueno

Affiliations

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Abstract

The F-ATPase is a rotary motor fueled by ATP hydrolysis. Its rotational dynamics have been well characterized using single-molecule rotation assays. While F-ATPases from various species have been studied using rotation assays, the standard model for single-molecule studies has been the F-ATPase from thermophilic sp. PS3, named TF. Single-molecule studies of TF have revealed fundamental features of the F-ATPase, such as the principal stoichiometry of chemo-mechanical coupling (hydrolysis of 3 ATP per turn), torque (approximately 40 pN·nm), and work per hydrolysis reaction (80 pN·nm = 48 kJ/mol), which is nearly equivalent to the free energy of ATP hydrolysis. Rotation assays have also revealed that TF exhibits two stable conformational states during turn: a binding dwell state and a catalytic dwell state. Although many structures of F have been reported, most of them represent the catalytic dwell state or its related states, and the structure of the binding dwell state remained unknown. A recent cryo-EM study on TF revealed the structure of the binding dwell state, providing insights into how F generates torque coupled to ATP hydrolysis. In this review, we discuss the torque generation mechanism of F based on the structure of the binding dwell state and single-molecule studies.

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