Hydrophobic mismatch sorts SNARE proteins into distinct membrane domains

Nat Commun. 2015 Jan 30;6:5984. doi: 10.1038/ncomms6984.

Abstract

The clustering of proteins and lipids in distinct microdomains is emerging as an important principle for the spatial patterning of biological membranes. Such domain formation can be the result of hydrophobic and ionic interactions with membrane lipids as well as of specific protein-protein interactions. Here using plasma membrane-resident SNARE proteins as model, we show that hydrophobic mismatch between the length of transmembrane domains (TMDs) and the thickness of the lipid membrane suffices to induce clustering of proteins. Even when the TMDs differ in length by only a single residue, hydrophobic mismatch can segregate structurally closely homologous membrane proteins in distinct membrane domains. Domain formation is further fine-tuned by interactions with polyanionic phosphoinositides and homo and heterotypic protein interactions. Our findings demonstrate that hydrophobic mismatch contributes to the structural organization of membranes.

Publication types

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

MeSH terms

  • Animals
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Antibody Technique
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Dynamics Simulation
  • Phosphatidylinositols / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • SNARE Proteins / chemistry*
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*

Substances

  • Phosphatidylinositols
  • SNARE Proteins