Partially inserted nascent chain unzips the lateral gate of the Sec translocon

EMBO Reports
Lukas KaterAlexej Kedrov

Abstract

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.

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Citations

Sep 14, 2019·EMBO Reports·Yoshiki Tanaka, Tomoya Tsukazaki
Dec 12, 2020·The EMBO Journal·Tsai-Hsuan WengRoland Beckmann
Jan 6, 2021·Nature Structural & Molecular Biology·Samuel ItskanovEunyong Park
Oct 16, 2020·The FEBS Journal·Sabrina KochArnold J M Driessen
Apr 19, 2021·Trends in Cell Biology·Madeline M DavisBarry D Bruce
May 4, 2021·Frontiers in Molecular Biosciences·Julia OswaldHans-Georg Koch
Jun 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Evan MercierMarina V Rodnina
Jul 28, 2021·The FEBS Journal·Michael KamelAlexej Kedrov
Mar 13, 2020·Journal of Chemical Information and Modeling·Shirin AkbarJayati Sengupta
Oct 13, 2021·ChemPlusChem·Ziqi Lyu, Joseph C Genereux

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Methods Mentioned

BETA
fluorescence imaging
PCR

Software Mentioned

memgen
Relion
‐ Tools
EM
LeaP
pmemd
phenix
ND
MotionCor2
UCSF Chimera

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