title: Three-dimensional model for meta-II rhodopsin, an activated G-protein-coupled receptor.
abstract: A novel approach that iteratively combined the results of energy calculations and experimental data was used to generate a three-dimensional (3D) model of the photoactivated state (R*) of bovine rhodopsin (Rh). The approach started with simplified energy calculations in an effort to find a set of sterically and energetically reasonable options for transmembrane (TM) helix arrangements with all-trans-retinal. Various 3D models of TM helix packing found by computations were then compared to limited site-directed spin-label experimental data regarding the transition of the TM helices of Rh in the inactive state (R) to those in the R* state to identify the most plausible model of the TM helical bundle. At the next step, all non-TM structural elements, such as the non-TM helix 8, the N- and C-terminal fragments, and the loops connecting TM helices, were reconstructed, and after the entire R* structure had been relaxed, all other currently available additional experimental data, both mutational and spectroscopic, on the structure of the meta-II state of rhodopsin were used to validate the resulting 3D model.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Nikiforovich
authors.forename: Garland R
authors.initials: GR
authors.lastname: Marshall
mesh_terms: D000818:Animals; D002417:Cattle; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008027:Light; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013113:Spin Labels; D013816:Thermodynamics
chemical_list: D004220:Disulfides; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D013113:Spin Labels; C013110:metarhodopsins; D012243:Rhodopsin; D020962:Heterotrimeric GTP-Binding Proteins; D003545:Cysteine