Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation (original) (raw)
Allen, WJ, Corey, RA, Oatley, P et al. (5 more authors) (2016)Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation. eLife, 5. e15598. ISSN: 2050-084X
Abstract
The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In 21 prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor- 22 protein SecA, in concert with the proton motive force (PMF). However, the mechanism through 23 which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. 24 Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY- 2 channel at long range, while substrates at the SecY-channel entrance feed back to regulate 3 nucleotide exchange by SecA. This two-way communication suggests a new, unifying 4 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of 5 polypeptide diffusion. The model represents a solution to the problem of transporting inherently 6 variable substrates such as polypeptides, and may underlie mechanisms of other motors that 7 translocate proteins and nucleic acids.
Metadata
| Item Type: | Article |
|---|---|
| Authors/Creators: | Allen, WJCorey, RAOatley, PSessions, RBBaldwin, SARadford, SE  https://orcid.org/0000-0002-3079-8039Tuma, R https://orcid.org/0000-0003-0047-0013Collinson, I |
| Copyright, Publisher and Additional Information: | © 2016, Allen 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. |
| Dates: | Accepted: 14 May 2016Published (online): 16 May 2016Published: 16 May 2016 |
| Institution: | The University of Leeds |
| Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
| Date Deposited: | 23 May 2016 10:04 |
| Last Modified: | 05 Oct 2017 16:20 |
| Published Version: | http://dx.doi.org/10.7554/eLife.15598 |
| Status: | Published |
| Publisher: | eLife Sciences Publications |
| Identification Number: | 10.7554/eLife.15598 |
| Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100010 |