ATP-induced Asymmetric Pre-protein Folding As a Driver of Protein Translocation Through the Sec Machinery

Overview

Journal Elife

Specialty Biology

Date 2019 Jan 3

PMID 30601115

Citations 20

Authors

Robin A Corey

Zainab Ahdash

Anokhi Shah

Euan Pyle

William J Allen

Tomas Fessl

Janet E Lovett

Argyris Politis

Ian Collinson

Affiliations

Soon will be listed here.

Abstract

Transport of proteins across membranes is a fundamental process, achieved in every cell by the 'Sec' translocon. In prokaryotes, SecYEG associates with the motor ATPase SecA to carry out translocation for pre-protein secretion. Previously, we proposed a Brownian ratchet model for transport, whereby the free energy of ATP-turnover favours the directional diffusion of the polypeptide (Allen et al., 2016). Here, we show that ATP enhances this process by modulating secondary structure formation within the translocating protein. A combination of molecular simulation with hydrogendeuterium-exchange mass spectrometry and electron paramagnetic resonance spectroscopy reveal an asymmetry across the membrane: ATP-induced conformational changes in the cytosolic cavity promote unfolded pre-protein structure, while the exterior cavity favours its formation. This ability to exploit structure within a pre-protein is an unexplored area of protein transport, which may apply to other protein transporters, such as those of the endoplasmic reticulum and mitochondria.

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.

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.

Structural basis of SecA-mediated protein translocation.

Dong L, Yang S, Chen J, Wu X, Sun D, Song C Proc Natl Acad Sci U S A. 2023; 120(2):e2208070120.

PMID: 36598944 PMC: 9926265. DOI: 10.1073/pnas.2208070120.

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