ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery
- University of Bristol, United Kingdom
- King's College London, United Kingdom
- University of St Andrews, United Kingdom
- University of South Bohemia in Ceske Budejovice, Czech Republic
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.
Data availability
All data generated during this study are included in the Figures of the mansucript. EPR data is available at https://doi.org/10.17630/0fedaeec-7e27-4876-a6d1-cda2d3a6799c.
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EPR data from ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinerydoi:10.17630/0fedaeec-7e27-4876-a6d1-cda2d3a6799c.
Article and author information
Author details
William John Allen
Funding
Biotechnology and Biological Sciences Research Council (BB/M003604/1)
- Robin A Corey
- William John Allen
- Ian Collinson
Wellcome (104632)
- William John Allen
- Ian Collinson
Royal Society (University Research Fellowship)
- Janet E Lovett
Wellcome (109854/Z/15/Z)
- Zainab Ahdash
- Argyris Politis
Wellcome (099149/Z/12/Z)
- Anokhi Shah
- Janet E Lovett
European Regional Development Fund (CZ.02.1.01/0.0/0.0/15_003/0000441)
- Tomas Fessl
Engineering and Physical Sciences Research Council (ep/m508214/1)
- Anokhi Shah
Biotechnology and Biological Sciences Research Council (BB/I008675/1)
- Robin A Corey
- William John Allen
- Ian Collinson
Biotechnology and Biological Sciences Research Council (BB/N015126/1)
- Robin A Corey
- William John Allen
- Ian Collinson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Corey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery
eLife 8:e41803.
https://doi.org/10.7554/eLife.41803
