title: Transmembrane helix-helix interactions: comparative simulations of the glycophorin a dimer.
abstract: The glycophorin helix dimer is a paradigm for the exploration of helix-helix interactions in integral membrane proteins. Two NMR structures of the dimer are known, one in a detergent micelle and one in a lipid bilayer. Multiple (4 x 50 ns) molecular dynamics simulations starting from each of the two NMR structures, with each structure in either a dodecyl phosphocholine (DPC) micelle or a dimyristoyl phosphatidylcholine (DMPC) bilayer, have been used to explore the conformational dynamics of the helix dimer. Analysis of the helix-helix interaction, mediated by the GxxxG sequence motif, suggests convergence of the simulations to a common model. This is closer to the NMR structure determined in a bilayer than to micelle structure. The stable dimer interface in the final simulation model is characterized by (i) Gly/Gly packing and (ii) Thr/Thr interhelix H-bonds. These results demonstrate the ability of extended molecular dynamics simulations in a lipid bilayer environment to refine membrane protein structures or models derived from experimental data obtained in protein/detergent micelles.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cuthbertson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bond
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D019281:Dimerization; D006021:Glycophorins / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D018583:Pliability; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D006021:Glycophorins; D008823:Micelles