Two-way Communication Between SecY and SecA Suggests a Brownian Ratchet Mechanism for Protein Translocation

Overview

Journal Elife

Specialty Biology

Date 2016 May 17

PMID 27183269

Citations 53

Authors

William John Allen

Robin Adam Corey

Peter Oatley

Richard Barry Sessions

Steve A Baldwin

Sheena E Radford

Roman Tuma

Ian Collinson

Affiliations

Soon will be listed here.

Abstract

The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor-protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY-channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids.

Citing Articles

AFM observation of protein translocation mediated by one unit of SecYEG-SecA complex.

Kanaoka Y, Mori T, Nagaike W, Itaya S, Nonaka Y, Kohga H Nat Commun. 2025; 16(1):225.

PMID: 39779699 PMC: 11711467. DOI: 10.1038/s41467-024-54875-x.

The Multifunctional Preprotein Binding Domain of SecA.

Giotas E, Aikaterini Kaplani S, Eleftheriadis N Chembiochem. 2024; 25(23):e202400621.

PMID: 39268627 PMC: 11610655. DOI: 10.1002/cbic.202400621.

Dynamic coupling of fast channel gating with slow ATP-turnover underpins protein transport through the Sec translocon.

Crossley J, Allen W, Watkins D, Sabir T, Radford S, Tuma R EMBO J. 2024; 43(1):1-13.

PMID: 38177311 PMC: 10883268. DOI: 10.1038/s44318-023-00004-1.

A unifying mechanism for protein transport through the core bacterial Sec machinery.

Allen W, Collinson I Open Biol. 2023; 13(8):230166.

PMID: 37643640 PMC: 10465204. DOI: 10.1098/rsob.230166.

Interaction of the periplasmic chaperone SurA with the inner membrane protein secretion (SEC) machinery.

Troman L, Alvira S, Daum B, Gold V, Collinson I Biochem J. 2023; 480(4):283-296.

PMID: 36701201 PMC: 9987972. DOI: 10.1042/BCJ20220480.

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