title: Unlocking the Bacterial SecY Translocon.
abstract: The Sec translocon performs protein secretion and membrane protein insertion at the plasma membrane of bacteria and archaea (SecYEG/β), and the endoplasmic reticular membrane of eukaryotes (Sec61). Despite numerous structures of the complex, the mechanism underlying translocation of pre-proteins, driven by the ATPase SecA in bacteria, remains unresolved. Here we present a series of biochemical and computational analyses exploring the consequences of signal sequence binding to SecYEG. The data demonstrate that a signal sequence-induced movement of transmembrane helix 7 unlocks the translocon and that this conformational change is communicated to the cytoplasmic faces of SecY and SecE, involved in SecA binding. Our findings progress the current understanding of the dynamic action of the translocon during the translocation initiation process. The results suggest that the converging effects of the signal sequence and SecA at the cytoplasmic face of SecYEG are decisive for the intercalation and translocation of pre-protein through the SecY channel.
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Corey
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: Allen
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Komar
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Simonas
authors.initials: S
authors.lastname: Masiulis
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Menzies
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Robson
authors.affiliation: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK. Electronic address: ian.collinson@bristol.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Collinson
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics*; D017433:Protein Structure, Secondary; D021381:Protein Transport; D000069816:SEC Translocation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000081416:SecA Proteins
chemical_list: D001426:Bacterial Proteins; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins