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.
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August 2007
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Conference Article|
July 20 2007
Ligand binding and activation of the CGRP receptor
A.C. Conner;
A.C. Conner
*School of Medicine, University of Swansea, Swansea SA2 8PP, U.K.
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J. Simms;
J. Simms
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
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J. Barwell;
J. Barwell
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
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M. Wheatley;
M. Wheatley
‡School of Biosciences, University of Birmingham, Birmingham B15 2TT, U.K.
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D.R. Poyner
D.R. Poyner
1
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
1To whom correspondence should be addressed (email D.R.Poyner@aston.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 26 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 729–732.
Article history
Received:
April 26 2007
Citation
A.C. Conner, J. Simms, J. Barwell, M. Wheatley, D.R. Poyner; Ligand binding and activation of the CGRP receptor. Biochem Soc Trans 1 August 2007; 35 (4): 729–732. doi: https://doi.org/10.1042/BST0350729
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