The receptor for calcitonin-gene-related peptide (CGRP) is a heterodimer formed by calcitonin-receptor-like receptor (CRLR), a type II (family B) G-protein-coupled receptor, and receptor-activity-modifying protein 1 (RAMP1), a single-membrane-pass protein. It is likely that the first seven or so amino acids of CGRP (which form a disulphide-bonded loop) interact with the transmembrane domain of CRLR to cause receptor activation. The rest of the CGRP molecule falls into three domains. Residues 28-37 and 8-18 are normally required for high-affinity binding, while residues 19-27 form a hinge region. The 28-37 region is almost certainly in direct contact with the receptor; 8-18 may make additional receptor contacts or may stabilize an appropriate conformation of 28-37. It is likely that these regions of CGRP interact both with CRLR and with the extracellular domain of RAMP1.
Bibliographical noteColloquium on Lessons from the Type II Family of G-Protein-Coupled Receptores - Their Ligands, Receptor Structure and Function, Edinburgh (UK), 8-10 April 2002
- calcitonin-receptor-like receptor (CRLR)
- receptor-activity-modifying protein 1 (RAMPI)
- structure-activity relationships
Conner, A. C., Hay, D. L., Howitt, S. G., Kilk, K., Langel, U., Wheatley, M., Smith, D. M., & Poyner, D. R. (2002). Interaction of calcitonin-gene-related peptide with its receptors. Biochemical Society Transactions, 30(4), 451-455. https://doi.org/10.1042/BST0300451