King's College London

Research portal

ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery

Research output: Contribution to journalArticle

Robin A. Corey, Zainab Ahdash, Anokhi Shah, Euan Pyle, William J. Allen, Tomas Fessl, Janet E. Lovett, Argyris Politis, Ian Collinson

Original languageEnglish
Article number41803
JournaleLife
Volume8
DOIs
Published2 Jan 2019

King's Authors

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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454