Ligand binding and activation of the CGRP receptor

James Barwell, John Simms, Alex Conner, Debbie Hay, Mark Wheatley, David Poyner

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Citation (Scopus)


The CGRP receptor is an atypical G-protein coupled receptor (GPCR), consisting of at least three proteins; a Family-B GPCR (calcitonin receptor-like receptor; CLR or CRLR), receptor activity modifying protein 1 (RAMP1) and receptor component protein (RCP). The extracellular domain of RAMP1 is tri-helical and possibly interacts with the extreme N-terminus of CLR to form the functional receptor. CGRP binding probably follows a two-step model of activation. The C-terminus of CGRP interacts with the N-terminus of the CLR/RAMP1 complex and its N-terminus interacts with the extracellular loops and of CLR to cause activation. The second and third extracellular loops are particularly important. During receptor activation TM helices 3 and 6 probably move apart. P343 in TM 6 is particularly important; E233 in TM3 and R173 and/or H178 in TM2 may form intermolecular interactions that may mirror the function of the DRY motif found in Family A GPCRs. Upon receptor activation the intracellular loops move to create a Gs-protein binding pocket.

Original languageEnglish
Title of host publicationThe Calcitonin Gene-related Peptide Family
Subtitle of host publicationForm, Function and Future Perspectives
EditorsDeborah L. Hay, Ian M. Dickerson
Place of PublicationNetherlands
PublisherSpringer Verlag
Number of pages18
ISBN (Electronic)9789048129096
ISBN (Print)9789048129089, 9789400791800
Publication statusPublished - 2010
Externally publishedYes


  • Alanine scan
  • CGRP binding
  • Family B GPCR
  • Molecular modelling
  • RAMP1
  • Receptor activation
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • Medicine(all)


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