A structural model of the active ribosome-bound membrane protein insertase YidC

Elife. 2014 Jul 10:3:e03035. doi: 10.7554/eLife.03035.

Abstract

The integration of most membrane proteins into the cytoplasmic membrane of bacteria occurs co-translationally. The universally conserved YidC protein mediates this process either individually as a membrane protein insertase, or in concert with the SecY complex. Here, we present a structural model of YidC based on evolutionary co-variation analysis, lipid-versus-protein-exposure and molecular dynamics simulations. The model suggests a distinctive arrangement of the conserved five transmembrane domains and a helical hairpin between transmembrane segment 2 (TM2) and TM3 on the cytoplasmic membrane surface. The model was used for docking into a cryo-electron microscopy reconstruction of a translating YidC-ribosome complex carrying the YidC substrate FOc. This structure reveals how a single copy of YidC interacts with the ribosome at the ribosomal tunnel exit and identifies a site for membrane protein insertion at the YidC protein-lipid interface. Together, these data suggest a mechanism for the co-translational mode of YidC-mediated membrane protein insertion.

Keywords: YidC; bioinformatics; cryo-EM; molecular dynamics; ribosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / chemistry*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Hydrogen Bonding
  • Kinetics
  • Lipids / chemistry
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Protein Biosynthesis
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Ribosomes / chemistry*
  • Ribosomes / metabolism
  • SEC Translocation Channels
  • Sequence Alignment
  • Thermodynamics

Substances

  • Escherichia coli Proteins
  • Lipids
  • Membrane Transport Proteins
  • SEC Translocation Channels
  • SecY protein, E coli
  • YIDC protein, E coli