title: Dynamic models of G-protein coupled receptor dimers: indications of asymmetry in the rhodopsin dimer from molecular dynamics simulations in a POPC bilayer.
abstract: Based on the growing evidence that G-protein coupled receptors (GPCRs) form homo- and hetero-oligomers, models of GPCR signaling are now considering macromolecular assemblies rather than monomers, with the homo-dimer regarded as the minimal oligomeric arrangement required for functional coupling to the G-protein. The dynamic mechanisms of such signaling assemblies are unknown. To gain some insight into properties of GPCR dimers that may be relevant to functional mechanisms, we study their current structural prototype, rhodopsin. We have carried out nanosecond time-scale molecular dynamics (MD) simulations of a rhodopsin dimer and compared the results to the monomer simulated in the same type of bilayer membrane model composed of an equilibrated unit cell of hydrated palmitoyl-oleoyl-phosphatidyl choline (POPC). The dynamic representation of the homo-dimer reveals the location of structural changes in several regions of the monomeric subunits. These changes appear to be more pronounced at the dimerization interface that had been shown to be involved in the activation process [Proc Natl Acad Sci USA 102:17495, 2005]. The results are consistent with a model of GPCR activation that involves allosteric modulation through a single GPCR subunit per dimer.
authors.affiliation: Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA. maf2037@med.cornell.edu
authors.forename: Marta
authors.initials: M
authors.lastname: Filizola
authors.forename: Simon X
authors.initials: SX
authors.lastname: Wang
authors.forename: Harel
authors.initials: H
authors.lastname: Weinstein
mesh_terms: D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D019281:Dimerization; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry*; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D021122:Protein Subunits; D012243:Rhodopsin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine