Ligand binding and activation of the CGRP receptor

A. C. Conner, J. Simms, J. Barwell, M. Wheatley, D. R. Poyner

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The receptor for CGRP (calcitonin gene-related peptide) is a heterodimer between a GPCR (G-protein-coupled receptor), CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). Models have been produced of RAMP1 and CLR. It is likely that the C-terminus of CGRP interacts with the extracellular N-termini of CLR and RAMP1; the extreme N-terminus of CLR is particularly important and may interact directly with CGRP and also with RAMP1. The N-terminus of CGRP interacts with the TM (transmembrane) portion of the receptor; the second ECL (extracellular loop) is especially important. Receptor activation is likely to involve the relative movements of TMs 3 and 6 to create a G-protein-binding pocket, as in Family A GPCRs. Pro321 in TM6 appears to act as a pivot. At the base of TMs 2 and 3, Arg151, His155 and Glu211 may form a loose equivalent of the Family A DRY (Asp-Arg-Tyr) motif. Although the details of this proposed activation mechanism clearly do not apply to all Family B GPCRs, the broad outlines may be conserved.

Original languageEnglish
Pages (from-to)729-732
Number of pages4
JournalBiochemical Society Transactions
Volume35
Issue number4
DOIs
Publication statusPublished - 20 Jul 2007
Externally publishedYes

Keywords

  • Adrenomedullin
  • Calcitonin receptor-like receptor
  • DRY motif
  • G-protein
  • Receptor activation
  • Receptor activity-modifying protein 1 (RAMP1)

ASJC Scopus subject areas

  • Biochemistry

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