YidC Insertase of Escherichia coli: Water Accessibility and Membrane Shaping

Structure. 2017 Sep 5;25(9):1403-1414.e3. doi: 10.1016/j.str.2017.07.008. Epub 2017 Aug 24.

Abstract

The YidC/Oxa1/Alb3 family of membrane proteins function to insert proteins into membranes in bacteria, mitochondria, and chloroplasts. Recent X-ray structures of YidC from Bacillus halodurans and Escherichia coli revealed a hydrophilic groove that is accessible from the lipid bilayer and the cytoplasm. Here, we explore the water accessibility within the conserved core region of the E. coli YidC using in vivo cysteine alkylation scanning and molecular dynamics (MD) simulations of YidC in POPE/POPG membranes. As expected from the structure, YidC possesses an aqueous membrane cavity localized to the membrane inner leaflet. Both the scanning data and the MD simulations show that the lipid-exposed transmembrane helices 3, 4, and 5 are short, leading to membrane thinning around YidC. Close examination of the MD data reveals previously unrecognized structural features that are likely important for protein stability and function.

Keywords: YidC; alkylation; aqueous access; cysteine-scanning mutagenesis; membrane protein folding; membrane protein insertion; membrane thinning; molecular dynamics.

MeSH terms

  • Alkylation
  • Cell Membrane / metabolism
  • Crystallography, X-Ray
  • Cysteine / chemistry
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Stability
  • Protein Structure, Secondary
  • Water / metabolism*

Substances

  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • YIDC protein, E coli
  • Water
  • Cysteine