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

RA. Corey, Z. Ahdash, A. Shah, E. Pyle, WJ. Allen, T. Fessl, JE. Lovett, A. Politis, I. Collinson,

. 2019 ; 8 (-) : . [pub] 20190102

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20022918

Grant support
BB/I008675/1 Biotechnology and Biological Sciences Research Council - United Kingdom
099149/Z/12/Z Wellcome - International
CZ.02.1.01/0.0/0.0/15_003/0000441 European Regional Development Fund - International
109854/Z/15/Z Wellcome - International
BB/N015126/1 Biotechnology and Biological Sciences Research Council - United Kingdom
Wellcome Trust - United Kingdom
104632 Wellcome - International
BB/M003604/1 Biotechnology and Biological Sciences Research Council - United Kingdom
ep/m508214/1 Engineering and Physical Sciences Research Council - International
University Research Fellowship Royal Society - International

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.

References provided by Crossref.org

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$a Ahdash, Zainab $u Department of Chemistry, King's College London, London, United Kingdom.
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$a Shah, Anokhi $u SUPA School of Physics and Astronomy and BSRC, University of St Andrews, Scotland, United Kingdom.
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$a Pyle, Euan $u Department of Chemistry, King's College London, London, United Kingdom. Department of Chemistry, Imperial College London, London, United Kingdom.
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