ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery
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.
Citation
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
Publication
eLife
Status
Peer reviewed
ISSN
2050-084XType
Journal article
Description
Funding: Royal Society for a University Research Fellowship; Wellcome Multi-User Equipment Grant (099149/Z/12/Z) (JEL).Collections
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