title: Molecular packing and packing defects in helical membrane proteins.
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.
authors.affiliation: Institute of Biochemistry Charité, University Medicine Berlin, 10117 Berlin, Germany. peter.hildebrand@charite.de
authors.forename: Peter Werner
authors.initials: PW
authors.lastname: Hildebrand
authors.forename: Kristian
authors.initials: K
authors.lastname: Rother
authors.forename: Andrean
authors.initials: A
authors.lastname: Goede
authors.forename: Robert
authors.initials: R
authors.lastname: Preissner
authors.forename: Cornelius
authors.initials: C
authors.lastname: Frömmel
mesh_terms: D003198:Computer Simulation; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D010539:Permeability; D016062:Porosity; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes