Locating ligand-binding sites in 7tm receptors by protein engineering

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Abstract

Over the past year, mutational analysis of peptide receptors has started to change our understanding of the interaction between G protein coupled receptors and their ligands, an area previously almost totally dominated by results from studies of monoamine receptors. A picture is currently emerging, in which small ligands appear to bind in three (more or less) overlapping ligand-binding pockets in between the transmembrane segments. In contrast, contact residues for peptide and protein ligands have mainly been found in exterior regions of peptide and protein receptors. It is also becoming increasingly clear that agonists and antagonists may interact in vastly different manners, even though they are competitive ligands for a common receptor.

References (102)

  • CJ Jensen et al.

    The Species Selectivity of Chemically Distinct Tachykinin Nonpeptide Antagonists is Dependent on Common Divergent Residues of the Rat and Human Neurokinin-1 Receptors

    Mol Pharmacol

    (1993)
  • L Wu et al.

    Identification of Methionine 124 and Alanine 146 in the Second Transmembrane Segment of the Human Tachykinin NK3 Receptor as Residues Involved in Species-Selective Binding to SR48968

    Biochem Biophys Res Commun

    (1994)
  • R Maggio et al.

    Coexpression Studies with Mutant Muscarinic/Adrenergic Receptors Provide Evidence for Intermolecular ‘Cross-Talk’ between G-Protein-Linked Receptors

  • TM Fong et al.

    Amino-Aromatic Interaction between Histidine 197 of the Neurokinin-1 Receptor and CP 96345

    Nature

    (1993)
  • SA Hjorth et al.

    Identification of Peptide Binding Residues in the Extracellular Domains of the AT1 Receptor

    J Biol Chem

    (1994)
  • CD Strader et al.

    Identification of Two Serine Residues Involved in Agonist Activation of the β-Adrenergic Receptor

    J Biol Chem

    (1989)
  • JP Huggins et al.

    Modelling and Modification of the Binding Site of Endothelin and Other Receptors

    Eur J Pharmacol

    (1993)
  • MW Dudly et al.

    Adenosine A1 Receptor and Ligand Molecular Modeling

    Drug Dev Res

    (1993)
  • BA Cox et al.

    Contributions of Conserved Serine Residues to the Interaction of Ligands with Dopamine D2 Receptors

    J Neurochem

    (1992)
  • A Mansour et al.

    Site-Directed Mutagenesis of the Human Dopamine D2 Receptor

    Eur J Pharmacol

    (1992)
  • NJ Pollock et al.

    Serine Mutations in Transmembrane V of the Dopamine D1 Receptor Affect Ligand Interactions and Receptor Activation

    J Biol Chem

    (1992)
  • TM Fong et al.

    The Role of Histidine 265 in Antagonist Binding to the Neurokinin-1 Receptor

    J Biol Chem

    (1994)
  • A Townsend-Nicholson et al.

    A Threonine Residue in the Seventh Transmembrane Domain of the Human A1 Adenosine Receptor Mediates Specific Agonist Binding

    J Biol Chem

    (1994)
  • D Oksenberg et al.

    A Single Amino-Acid Difference Confers Major Pharmacological Variation between Human and Rodent 5-HT1B Receptors

    Nature

    (1992)
  • A Smolyar et al.

    Role of Threonine 342 in Helix 7 of the 5-Hydroxytryptamine Type 1 D Receptor in Ligand Binding: An Indirect Mechanism for Receptor Selectivity

    Mol Pharmacol

    (1993)
  • SR Krystek et al.

    Mutation of Peptide Binding Site in Transmembrane Region of a G Protein-Coupled Receptor Accounts for Endothelin Receptor Subtype Selectivity

    J Biol Chem

    (1994)
  • GS Seetharamaiah et al.

    A Recombinant Extracellular Domain of the Thyrotropin (TSH) Receptor Binds TSH in the Absence of Membranes

    Endocrinology

    (1994)
  • CA Hébert et al.

    Partial Functional Mapping of the Human Interleukin-8 Type A Receptor

    J Biol Chem

    (1993)
  • P Walker et al.

    Acidic Residues in Extracellular Loops of the Human Y1 Neuropeptide Y Receptor are Essential for Ligand Binding

    J Biol Chem

    (1994)
  • SJ Siciliano et al.

    Two-Site Binding of C5a by its Receptor: An Alternative Binding Paradigm for G Protein-Coupled Receptors

  • ME Olah et al.

    Cloning, Expression and Characterization of the Unique Bovine A1 Adenosine Receptor-Studies of the Ligand Binding Site by Site-Directed Mutagenesis

    J Biol Chem

    (1992)
  • J Findley et al.

    Three-Dimensional Modelling of G Protein-Linked Receptors

    Trends Pharmacol Sci

    (1990)
  • TK Attword et al.

    Multiple Sequence Alignment of Protein Families Showing Low Sequence Homology: A Methodological Approach using Database Pattern-Matching Discriminators for G-Protein-Linked Receptors

    Gene

    (1991)
  • CD Strader et al.

    Structural Basis of β-Adrenergic Receptor Function

    FASEB J

    (1989)
  • HG Dohlman et al.

    Model Systems for the Study of Seven-Transmembrane Segment Receptors

    Annu Rev Biochem

    (1991)
  • B Kobilka

    Adrenergic Receptors as Models for G Protein-Coupled Receptors

    Annu Rev Neurosci

    (1992)
  • TM Savarese et al.

    In Vitro Mutagenesis and the Search for Structure-Function Relationships Among G Protein-Coupled Receptors

    Biochem J

    (1992)
  • AD Strosberg

    Structure, Function and Regulation of Adrenergic Receptors

    Protein Sci

    (1993)
  • GF Schertler et al.

    Projection Structure of Rhodopsin

    Nature

    (1993)
  • J Hoflack et al.

    Re-Evaluation of Bacteriorhodopsin as a Model for G Protein-Coupled Receptors

    Trends Pharmacol Sci

    (1994)
  • AP Ijzerman et al.

    Molecular Modeling of Adenosine Receptors. I. The Ligand Binding Site on the Al Receptor

    Drug Des Discov

    (1992)
  • P Cronet et al.

    Modeling of Transmembrane Seven Helix Bundles

    Protein Eng

    (1993)
  • MF Hibert et al.

    Three-Dimensional Models of Neurotransmitter G-Protein Coupled Receptors

    Mol Pharmacol

    (1991)
  • G Nordvall et al.

    Binding-Site Modeling of the Muscarinic m1 Receptor: A Combination of Homology-Based and Indirect Approaches

    J Med Chem

    (1993)
  • J Hoflack et al.

    Three-Dimensional Models of Gonado-Thyrotropin Hormone Receptor Transmembrane Domain

    Drug Des Discov

    (1993)
  • Y Yamamoto et al.

    Modeling of Human Thromboxane A2 Receptor and Analysis of the Receptor-Ligand Interaction

    J Med Chem

    (1993)
  • L Oliveira et al.

    A Common Step for Signal Transduction in G Protein-Coupled Receptors

    Trends Pharmacol Sci

    (1994)
  • JM Baldwin

    The Probable Arrangement of the Helices in G Protein-Coupled Receptors

    EMBO J

    (1993)
  • M Hibert et al.

    This is Not a G Protein-Coupled Receptor

    Trends Pharmacol Sci

    (1993)
  • S Zoffmann et al.

    Conserved His VI-17 of the NK-1 Receptor is Involved in Binding of Non-Peptide Antagonists but Not Substance P

    FEBS Lett

    (1993)

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