Projects per year
Abstract
The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor- protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. 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- channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids.
Original language | English |
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Article number | e15598 |
Number of pages | 23 |
Journal | eLife |
Volume | 5 |
Early online date | 16 May 2016 |
DOIs | |
Publication status | Published - 14 Jun 2016 |
Research Groups and Themes
- Bristol BioDesign Institute
Keywords
- synthetic biology
Fingerprint
Dive into the research topics of 'Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation'. Together they form a unique fingerprint.Projects
- 4 Finished
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CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
Project: Research
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Understanding the Mechanism of Membrane Protein Insertion
Collinson, I. R. (Principal Investigator)
1/10/14 → 28/02/18
Project: Research
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The UK High-End Computing Consortium for Biomolecular Simulation
Mulholland, A. J. (Principal Investigator)
1/11/13 → 31/01/19
Project: Research
Equipment
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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility
Profiles
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Dr Richard B Sessions
- School of Biochemistry - Honorary Senior Research Fellow
Person: Honorary and Visiting Academic