Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation

William Allen, Robin Corey, Peter Oatley, Richard Sessions, Steve A. Baldwin, Sheena E. Radford, Roman Tuma, Ian Collinson

Research output: Contribution to journalArticle (Academic Journal)peer-review

78 Citations (Scopus)
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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 languageEnglish
Article numbere15598
Number of pages23
Early online date16 May 2016
Publication statusPublished - 14 Jun 2016


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