Agonist binding to peptide hormone receptors

M. Wheatley, S. R. Hawtin, V. J. Wesley, H. C. Howard, J. Simms, A. Miles, K. McEwan, R. A. Parslow

Research output: Contribution to journalConference article

11 Citations (Scopus)

Abstract

A fundamental issue in molecular pharmacology is to define how agonist-receptor interaction differs from that of antagonist-receptor interaction. The V1a vasopressin receptor (V1aR) is a member of a family of related G-protein-coupled receptors (GPCRs) that are activated by vasopressin, oxytocin (OT) and related peptides. A segment of the N-terminus that was required for agonist binding, but not antagonist binding, was identified by characterizing truncated V1aR constructs. Site-directed mutagenesis revealed that a single residue (Arg46) was critical for agonist binding and receptor activation. The N-terminus of the related OT receptor (OTR) could recover agonist binding in a chimaeric OTRN-V1aR construct. Furthermore, Arg34 of the human OTR, which corresponds to Arg46 of the rat V1aR, provided agonist-specific binding epitopes in the OTR, indicating a conserved function of this locus throughout this GPCR subfamily. Mutation of Arg46 revealed that high-affinity agonist binding had an absolute requirement for arginine at this position.

Original languageEnglish
Pages (from-to)35-39
Number of pages5
JournalBiochemical Society Transactions
Volume31
Issue number1
DOIs
Publication statusPublished - Feb 2003
Externally publishedYes

Keywords

  • G-protein-coupled receptor
  • Oxytocin receptor
  • Receptor activation
  • Vasopressin receptor

ASJC Scopus subject areas

  • Biochemistry

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