Interaction of calcitonin-gene-related peptide with its receptors.
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.
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
A C
AC
Conner
D L
DL
Hay
S G
SG
Howitt
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K
Kilk
U
U
Langel
M
M
Wheatley
D M
DM
Smith
D R
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Poyner
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000737:chemistry* / Q000502:physiology*
D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide