Three-dimensional structure for the beta 2 adrenergic receptor protein based on computer modeling studies.

Computer-aided model building techniques have been used to construct three-dimensional model structures for hamster beta 2 adrenergic receptor. Experimental data were used as constraints to guide the model building procedure, and a number of rather strict criteria were applied to assess the physical plausibility of model structures. We present details of our best model structure to date, which is consistent with a large body of experimental data. We also discuss in detail our model building procedures and evaluation criteria, which we believe may be of general utility in modeling projects.

[1]  M. Caron,et al.  A family of receptors coupled to guanine nucleotide regulatory proteins. , 1987, Biochemistry.

[2]  Irving S. Sigal,et al.  Structure-Function Analysis of the β-Adrenergic Receptor , 1988 .

[3]  D. Eisenberg,et al.  The hydrophobic moment detects periodicity in protein hydrophobicity. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Strader,et al.  Mutations that uncouple the beta-adrenergic receptor from Gs and increase agonist affinity. , 1987, The Journal of biological chemistry.

[5]  C. Strader,et al.  Conserved aspartic acid residues 79 and 113 of the beta-adrenergic receptor have different roles in receptor function. , 1988, The Journal of biological chemistry.

[6]  P. Y. Chou,et al.  Prediction of the secondary structure of proteins from their amino acid sequence. , 2006 .

[7]  T. Lybrand,et al.  PAP : a protein analysis package. , 1990 .

[8]  E. Neumann,et al.  Structural heterogeneity of membrane receptors and GTP-binding proteins and its functional consequences for signal transduction. , 1991, European journal of biochemistry.

[9]  C. Strader,et al.  Characterization of the binding domain of the beta-adrenergic receptor with the fluorescent antagonist carazolol. Evidence for a buried ligand binding site. , 1990, The Journal of biological chemistry.

[10]  J. Deisenhofer,et al.  Structure of the protein subunits in the photosynthetic reaction centre of Rhodopseudomonas viridis at 3Å resolution , 1985, Nature.

[11]  M. Caron,et al.  Structural basis of beta-adrenergic receptor subtype specificity studied with chimeric beta 1/beta 2-adrenergic receptors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Ponder,et al.  Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. , 1987, Journal of molecular biology.

[13]  C. Strader,et al.  Genetic analysis of the molecular basis for β‐adrenergic receptor subtype specificity , 1989, Proteins.

[14]  R. Henderson,et al.  Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. , 1990, Journal of molecular biology.

[15]  C. Strader,et al.  Structural features required for ligand binding to the beta‐adrenergic receptor. , 1987, The EMBO journal.

[16]  C. Strader,et al.  Identification and sequence of a binding site peptide of the beta 2-adrenergic receptor. , 1988, Biochemistry.

[17]  C. Strader,et al.  Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor. , 1989, The Journal of biological chemistry.

[18]  Hong Wang,et al.  Site-directed anti-peptide antibodies define the topography of the beta-adrenergic receptor. , 1989, The Journal of biological chemistry.

[19]  F E Cohen,et al.  Novel method for the rapid evaluation of packing in protein structures. , 1990, Journal of molecular biology.

[20]  A. Gilman,et al.  G proteins: transducers of receptor-generated signals. , 1987, Annual review of biochemistry.

[21]  C. Strader,et al.  Specific activation of Gs by synthetic peptides corresponding to an intracellular loop of the β‐adrenergic receptor , 1991, FEBS letters.

[22]  M. Hollenberg.  Structure‐activity relationships for transmembrane signaling: the receptor's turn , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  H. Hebert,et al.  The molecular structure of adrenergic and dopaminergic substances , 1979, Quarterly Reviews of Biophysics.

[24]  J. Garnier,et al.  Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. , 1978, Journal of molecular biology.

[25]  D. Eisenberg,et al.  Analysis of membrane and surface protein sequences with the hydrophobic moment plot. , 1984, Journal of molecular biology.

[26]  M. S. Tute,et al.  A molecular modelling study of the interaction of noradrenaline with theβ2-adrenergic receptor , 1989, J. Comput. Aided Mol. Des..

[27]  G. Petsko,et al.  Weakly polar interactions in proteins. , 1988, Advances in protein chemistry.

[28]  E. Eliopoulos,et al.  Three-dimensional modelling of G protein-linked receptors. , 1990, Trends in pharmacological sciences.

[29]  J. Deisenhofer,et al.  The Photosynthetic Reaction Center from the Purple Bacterium Rhodopseudomonas viridis , 1989, Science.

[30]  M. Caron,et al.  Covalent labeling of the beta-adrenergic ligand-binding site with para-(bromoacetamidyl)benzylcarazolol. A highly potent beta-adrenergic affinity label. , 1985, Molecular pharmacology.

[31]  J Hoflack,et al.  Three-dimensional models of neurotransmitter G-binding protein-coupled receptors. , 1991, Molecular pharmacology.

[32]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[33]  C. Chothia,et al.  Structure of proteins: packing of alpha-helices and pleated sheets. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Conrad C. Huang,et al.  The MIDAS display system , 1988 .

[35]  I. Sylte,et al.  Molecular dynamics of dopamine at the D2 receptor. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Kerlavage,et al.  Molecular biology of adrenergic and muscarinic cholinergic receptors. A perspective. , 1989, Biochemical pharmacology.

[37]  P. Kollman,et al.  An all atom force field for simulations of proteins and nucleic acids , 1986, Journal of computational chemistry.