Molecular packing and packing defects in helical membrane proteins

Biophys J. 2005 Mar;88(3):1970-7. doi: 10.1529/biophysj.104.049585. Epub 2004 Nov 19.

Abstract

The packing of helices spanning lipid bilayers is crucial for the stability and function of alpha-helical membrane proteins. Using a modified Voronoi procedure, we calculated packing densities for helix-helix contacts in membrane spanning domains. Our results show that the transmembrane helices of protein channels and transporters are significantly more loosely packed compared with helices in globular proteins. The observed packing deficiencies of these membrane proteins are also reflected by a higher amount of cavities at functionally important sites. The cavities positioned along the gated pores of membrane channels and transporters are noticeably lined by polar amino acids that should be exposed to the aqueous medium when the protein is in the open state. In contrast, nonpolar amino acids surround the cavities in those protein regions where large rearrangements are supposed to take place, as near the hinge regions of transporters or at restriction sites of protein channels. We presume that the observed deficiencies of helix-helix packing are essential for the helical mobility that sustains the function of many membrane protein channels and transporters.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Ion Channels / chemistry
  • Lipid Bilayers / chemistry*
  • Membrane Fluidity*
  • Membrane Proteins / chemistry*
  • Membrane Transport Proteins / chemistry
  • Models, Chemical*
  • Models, Molecular*
  • Multiprotein Complexes / chemistry*
  • Permeability
  • Porosity
  • Protein Conformation
  • Protein Structure, Secondary

Substances

  • Ion Channels
  • Lipid Bilayers
  • Membrane Proteins
  • Membrane Transport Proteins
  • Multiprotein Complexes