Combined biophysical and biochemical information confirms arrangement of transmembrane helices visible from the three-dimensional map of frog rhodopsin.

The electron density projection map of frog rhodopsin at 6 A resolution had been until recently the most direct evidence for the three-dimensional structure of a transmembrane domain of any G-protein-coupled receptor. Only three out of seven transmembrane helices are clearly defined, whilst the other four are hidden in a patch of unresolved electron density. A model of the seven-helix bundle has been created by generating positions and orientations for the four unresolved helices through performing a conformational search directed by structural restraints derived from other experimental data. These four helices are significantly tilted with respect to the membrane normal, and the cytosolic end of helix C is inserted between helices D and E. These calculations produce positions and orientations for these additional helices that are consistent with the recently published low-resolution three-dimensional map, and provide a template for more detailed modelling of rhodopsin structure and function.

[1]  T. Sakmar,et al.  Spectroscopic evidence for interaction between transmembrane helices 3 and 5 in rhodopsin. , 1998, Biochemistry.

[2]  P Herzyk,et al.  Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban. , 1998, Biophysical journal.

[3]  A. Watts,et al.  Photoreceptor rhodopsin: structural and conformational study of its chromophore 11‐cis retinal in oriented membranes by deuterium solid state NMR , 1998, FEBS letters.

[4]  P Herzyk,et al.  Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide. , 1997, Journal of molecular graphics & modelling.

[5]  J. Baldwin,et al.  An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. , 1997, Journal of molecular biology.

[6]  Gebhard F. X. Schertler,et al.  Arrangement of rhodopsin transmembrane α-helices , 1997, Nature.

[7]  A. Lomize,et al.  The transmembrane 7-alpha-bundle of rhodopsin: distance geometry calculations with hydrogen bonding constraints. , 1997, Biophysical journal.

[8]  T. Sakmar,et al.  The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin* , 1996, The Journal of Biological Chemistry.

[9]  T. Sakmar,et al.  Functional Interaction of Transmembrane Helices 3 and 6 in Rhodopsin , 1996, The Journal of Biological Chemistry.

[10]  O. Lichtarge,et al.  Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F , 1996, Nature.

[11]  H. Khorana,et al.  Structural features and light-dependent changes in the cytoplasmic interhelical E-F loop region of rhodopsin: a site-directed spin-labeling study. , 1996, Biochemistry.

[12]  M. Karplus,et al.  Simulation of activation free energies in molecular systems , 1996 .

[13]  A. Scheer,et al.  Constitutively active mutants of the alpha 1B‐adrenergic receptor: role of highly conserved polar amino acids in receptor activation. , 1996, The EMBO journal.

[14]  P. Hargrave,et al.  Projection structure of frog rhodopsin in two crystal forms. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P Herzyk,et al.  Automated method for modeling seven-helix transmembrane receptors from experimental data. , 1995, Biophysical journal.

[16]  H. Khorana,et al.  Mapping light-dependent structural changes in the cytoplasmic loop connecting helices C and D in rhodopsin: a site-directed spin labeling study. , 1995, Biochemistry.

[17]  S. O. Smith,et al.  NMR constraints on the location of the retinal chromophore in rhodopsin and bathorhodopsin. , 1995, Biochemistry.

[18]  J. Ballesteros,et al.  [19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors , 1995 .

[19]  Jeremy C. Smith,et al.  Functional interactions in bacteriorhodopsin: a theoretical analysis of retinal hydrogen bonding with water. , 1995, Biophysical journal.

[20]  K. Nakanishi,et al.  The Location of the Chromophore in Rhodopsin - A Photoaffinity Study , 1994 .

[21]  M. Sansom,et al.  Parallel helix bundles and ion channels: molecular modeling via simulated annealing and restrained molecular dynamics. , 1994, Biophysical journal.

[22]  K. Fahmy,et al.  A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin. , 1994, The Journal of biological chemistry.

[23]  K. Fahmy,et al.  Characterization of rhodopsin-transducin interaction: a mutant rhodopsin photoproduct with a protonated Schiff base activates transducin. , 1994, Biochemistry.

[24]  S. Kaushal,et al.  Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa. , 1994, Biochemistry.

[25]  D. Oprian,et al.  Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness , 1994, Nature.

[26]  Gert Vriend,et al.  A common motif in G-protein-coupled seven transmembrane helix receptors , 1993, J. Comput. Aided Mol. Des..

[27]  S. O. Smith,et al.  Localization of the retinal protonated Schiff base counterion in rhodopsin. , 1993, Biophysical journal.

[28]  D. Oprian,et al.  Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness , 1993, Nature Genetics.

[29]  Gebhard F. X. Schertler,et al.  Projection structure of rhodopsin , 1993, Nature.

[30]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[31]  J. Baldwin.  The probable arrangement of the helices in G protein‐coupled receptors. , 1993, The EMBO journal.

[32]  T. Sakmar,et al.  Movement of the retinylidene Schiff base counterion in rhodopsin by one helix turn reverses the pH dependence of the metarhodopsin I to metarhodopsin II transition. , 1993, The Journal of biological chemistry.

[33]  S. Vishveshwara,et al.  Geometry of proline-containing alpha-helices in proteins. , 2009, International journal of peptide and protein research.

[34]  T J Oldfield,et al.  SQUID: a program for the analysis and display of data from crystallography and molecular dynamics. , 1992, Journal of molecular graphics.

[35]  D. Oprian,et al.  Changing the location of the Schiff base counterion in rhodopsin. , 1992, Biochemistry.

[36]  T. Sakmar,et al.  Introduction of hydroxyl-bearing amino acids causes bathochromic spectral shifts in rhodopsin. Amino acid substitutions responsible for red-green color pigment spectral tuning. , 1992, The Journal of biological chemistry.

[37]  D. Oprian,et al.  The ligand-binding domain of rhodopsin and other G protein-linked receptors , 1992, Journal of bioenergetics and biomembranes.

[38]  J. Nathans,et al.  Histidine residues regulate the transition of photoexcited rhodopsin to its active conformation, metarhodopsin II , 1992, Neuron.

[39]  Axel T. Brunger,et al.  X-PLOR Version 3.1: A System for X-ray Crystallography and NMR , 1992 .

[40]  A T Brünger,et al.  Automated modeling of coiled coils: application to the GCN4 dimerization region. , 1991, Protein engineering.

[41]  G H Jacobs,et al.  Spectral tuning of pigments underlying red-green color vision. , 1991, Science.

[42]  H. Khorana,et al.  Mapping of the amino acids in membrane-embedded helices that interact with the retinal chromophore in bovine rhodopsin. , 1991, The Journal of biological chemistry.

[43]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[44]  C. D. Gelatt,et al.  Optimization by Simulated Annealing , 1983, Science.

[45]  E. Dratz,et al.  The structure of rhodopsin and the rod outer segment disk membrane , 1983 .

[46]  P. Liebman.  In situ microspectrophotometric studies on the pigments of single retinal rods. , 1962, Biophysical journal.

[47]  N. Metropolis,et al.  Equation of State Calculations by Fast Computing Machines , 1953, Resonance.