title: Structure of the Sec61 channel opened by a signal sequence.
abstract: Secreted and integral membrane proteins compose up to one-third of the biological proteome. These proteins contain hydrophobic signals that direct their translocation across or insertion into the lipid bilayer by the Sec61 protein-conducting channel. The molecular basis of how hydrophobic signals within a nascent polypeptide trigger channel opening is not understood. Here, we used cryo-electron microscopy to determine the structure of an active Sec61 channel that has been opened by a signal sequence. The signal supplants helix 2 of Sec61α, which triggers a rotation that opens the central pore both axially across the membrane and laterally toward the lipid bilayer. Comparisons with structures of Sec61 in other states suggest a pathway for how hydrophobic signals engage the channel to gain access to the lipid bilayer.
authors.affiliation: MRC Laboratory of Molecular Biology, Medical Research Council, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Voorhees
authors.affiliation: MRC Laboratory of Molecular Biology, Medical Research Council, Francis Crick Avenue, Cambridge CB2 0QH, UK. rhegde@mrc-lmb.cam.ac.uk.
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004285:Dogs; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D021382:Protein Sorting Signals; D017433:Protein Structure, Secondary; D012270:Ribosomes / Q000737:chemistry; D000069816:SEC Translocation Channels
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels