Cryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch

Meghna Sobti,Alastair G Stewart,James L Walshe,Richard M Berry,Robert Ishmukhametov,Carol V Robinson,Di Wu,Yi C Zeng

doi:10.1038/s41467-020-16387-2

Meghna Sobti, Alastair G Stewart + Show 6 more

Open Access

https://doi.org/10.1038/s41467-020-16387-2

Copy DOI

Abstract

F1Fo ATP synthase functions as a biological rotary generator that makes a major contribution to cellular energy production. It comprises two molecular motors coupled together by a central and a peripheral stalk. Proton flow through the Fo motor generates rotation of the central stalk, inducing conformational changes in the F1 motor that catalyzes ATP production. Here we present nine cryo-EM structures of E. coli ATP synthase to 3.1–3.4 Å resolution, in four discrete rotational sub-states, which provide a comprehensive structural model for this widely studied bacterial molecular machine. We observe torsional flexing of the entire complex and a rotational sub-step of Fo associated with long-range conformational changes that indicates how this flexibility accommodates the mismatch between the 3- and 10-fold symmetries of the F1 and Fo motors. We also identify density likely corresponding to lipid molecules that may contribute to the rotor/stator interaction within the Fo motor.

Highlights

F1Fo adenosine tri-phosphate (ATP) synthase functions as a biological rotary generator that makes a major contribution to cellular energy production
In addition to generating a comprehensive structural model of E. coli F1Fo ATP synthase that provides a framework to interpret mutagenesis studies, we describe torsional flexing of the complex and a rotational sub-step of the Fo motor c-ring associated with long-range conformational changes
Cryo-EM maps of cysteine free E. coli F1Fo ATP synthase in the presence of 10 mM MgADP were obtained at 300 kV using methods similar to those in previous studies[14,15] (Fig. 1 and Supplementary Figs. 1 and 2)

Summary

Introduction

F1Fo ATP synthase functions as a biological rotary generator that makes a major contribution to cellular energy production. In addition to generating a comprehensive structural model of E. coli F1Fo ATP synthase that provides a framework to interpret mutagenesis studies, we describe torsional flexing of the complex and a rotational sub-step of the Fo motor c-ring associated with long-range conformational changes. These data indicate a model of how elastic coupling between the F1 and Fo motors is mediated by a dynamic, flexible peripheral stalk

Methods

Results

Conclusion