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TitlePartially inserted nascent chain unzips the lateral gate of the Sec translocon.
Journal, issue, pagesEMBO Rep., Vol. 20, Issue 10, Page e48191, Year 2019
Publish dateOct 4, 2019
AuthorsLukas Kater / Benedikt Frieg / Otto Berninghausen / Holger Gohlke / Roland Beckmann / Alexej Kedrov /
PubMed AbstractThe Sec translocon provides the lipid bilayer entry for ribosome-bound nascent chains and thus facilitates membrane protein biogenesis. Despite the appreciated role of the native environment in the ...The Sec translocon provides the lipid bilayer entry for ribosome-bound nascent chains and thus facilitates membrane protein biogenesis. Despite the appreciated role of the native environment in the translocon:ribosome assembly, structural information on the complex in the lipid membrane is scarce. Here, we present a cryo-electron microscopy-based structure of bacterial translocon SecYEG in lipid nanodiscs and elucidate an early intermediate state upon insertion of the FtsQ anchor domain. Insertion of the short nascent chain causes initial displacements within the lateral gate of the translocon, where α-helices 2b, 7, and 8 tilt within the membrane core to "unzip" the gate at the cytoplasmic side. Molecular dynamics simulations demonstrate that the conformational change is reversed in the absence of the ribosome, and suggest that the accessory α-helices of SecE subunit modulate the lateral gate conformation. Site-specific cross-linking validates that the FtsQ nascent chain passes the lateral gate upon insertion. The structure and the biochemical data suggest that the partially inserted nascent chain remains highly flexible until it acquires the transmembrane topology.
External linksPubMed:31379073 / Publisher's page
KeywordsCryoelectron Microscopy / Escherichia coli / Fluorescent Dyes / Lipid Bilayers / Molecular Dynamics Simulation / Peptides / Protein Conformation / Ribosomes / SEC Translocation Channels / MEMBRANE PROTEIN / monomeric translocon / nanodisc / insertion intermediate
MethodsEM (single particle)
Resolution6 A
Structure data

EMDB-4743:
Ribosome-bound SecYEG translocon in a nanodisc

PDB-6r7l:
Ribosome-bound SecYEG translocon in a nanodisc

Source
  • escherichia coli (E. coli)

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