ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery
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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.
Corey , R , Ahdash , Z , Shah , A , Pyle , E , Allen , W , Fessl , T , Lovett , J E , Politis , A & Collinson , I 2019 , ' ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery ' , eLife , vol. 8 , e41803 . https://doi.org/10.7554/eLife.41803
Copyright 2019 Corey et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DescriptionFunding: Royal Society for a University Research Fellowship; Wellcome Multi-User Equipment Grant (099149/Z/12/Z) (JEL).
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