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

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Robin Corey, Zainab Ahdash, Anokhi Shah, Euan Pyle, William Allen, Thomas Fessl, Janet Eleanor Lovett, Argyris Politis, Ian Collinson

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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. eLife 2016]. Here, we show that ATP enhances this process by modulating secondary structure formation within the translocating protein. A combination of molecular simulation with hydrogen-deuterium-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.
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Original languageEnglish
Article numbere41803
Number of pages25
JournaleLife
Volume8
DOIs
Publication statusPublished - 2 Jan 2019

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