4CG6: Cryo-em Of The Sec61-complex Bound To The 80s Ribosome Translating A Membrane-inserting Substrate

Citation:
Abstract
The biogenesis of secretory as well as transmembrane proteins requires the activity of the universally conserved protein-conducting channel (PCC), the Sec61 complex (SecY complex in bacteria). In eukaryotic cells the PCC is located in the membrane of the endoplasmic reticulum where it can bind to translating ribosomes for co-translational protein transport. The Sec complex consists of three subunits (Sec61alpha, beta and gamma) and provides an aqueous environment for the translocation of hydrophilic peptides as well as a lateral opening in the Sec61alpha subunit that has been proposed to act as a gate for the membrane partitioning of hydrophobic domains. A plug helix and a so-called pore ring are believed to seal the PCC against ion flow and are proposed to rearrange for accommodation of translocating peptides. Several crystal and cryo-electron microscopy structures revealed different conformations of closed and partially open Sec61 and SecY complexes. However, in none of these samples has the translocation state been unambiguously defined biochemically. Here we present cryo-electron microscopy structures of ribosome-bound Sec61 complexes engaged in translocation or membrane insertion of nascent peptides. Our data show that a hydrophilic peptide can translocate through the Sec complex with an essentially closed lateral gate and an only slightly rearranged central channel. Membrane insertion of a hydrophobic domain seems to occur with the Sec complex opening the proposed lateral gate while rearranging the plug to maintain an ion permeability barrier. Taken together, we provide a structural model for the basic activities of the Sec61 complex as a protein-conducting channel.
PDB ID: 4CG6Download
MMDB ID: 117185
PDB Deposition Date: 2013/11/21
Updated in MMDB: 2017/09
Experimental Method:
electron microscopy
Resolution: 7.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4CG6: tetrameric; determined by author and by software (PISA)
Molecular Components in 4CG6
Label Count Molecule
Proteins (4 molecules)
1
Protein Transport Protein Sec61 Subunit Alpha Isoform 1(Gene symbol: SEC61A1)
Molecule annotation
1
Protein Transport Protein Sec61 Subunit Gamma(Gene symbol: SEC61G)
Molecule annotation
1
Protein Transport Protein Sec61 Subunit Beta(Gene symbol: SEC61B)
Molecule annotation
1
Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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