Structure-activity relationships for α-calcitonin gene-related peptide

Harriet A. Watkins, Dan L. Rathbone, James Barwell, Debbie L. Hay, David R Poyner

Research output: Contribution to journalArticle

Abstract

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin (CT) family of peptides. It is a widely distributed neuropeptide implicated in conditions such as neurogenic inflammation. With other members of the CT family, it shares an N-terminal disulphide-bonded ring which is essential for biological activity, an area of potential α-helix, and a C-terminal amide. CGRP binds to the calcitonin receptor-like receptor (CLR) in complex with receptor activity-modifying protein 1 (RAMP1), a member of the family B (or secretin-like) GPCRs. It can also activate other CLR or calcitonin-receptor/RAMP complexes. This 37 amino acid peptide comprises the N-terminal ring that is required for receptor activation (residues 1-7); an α-helix (residues 8-18), a region incorporating a β-bend (residues 19-26) and the C-terminal portion (residues 27-37), that is characterized by bends between residues 28-30 and 33-34. A few residues have been identified that seem to make major contributions to receptor binding and activation, with a larger number contributing either to minor interactions (which collectively may be significant), or to maintaining the conformation of the bound peptide. It is not clear if CGRP follows the pattern of other family B GPCRs in binding largely as an α-helix. Linked Articles This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
LanguageEnglish
Pages1308-1322
Number of pages15
JournalBritish Journal of Pharmacology
Volume170
Issue number7
Early online date14 Nov 2012
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Calcitonin Gene-Related Peptide
Structure-Activity Relationship
Calcitonin Receptor-Like Protein
Calcitonin
Neuropeptides
Peptides
Receptor Activity-Modifying Protein 1
Calcitonin Receptors
Neurogenic Inflammation
Secretin
Amides
Disulfides
Pharmacology
Amino Acids
alpha-Helical Protein Conformation

Keywords

  • calcitonin
  • CGRP
  • adrenomedullin
  • amylin
  • helix-cap
  • receptor activation
  • domain
  • juxtamembrane
  • GPCR
  • RAMP
  • receptor activity-modifying protein

Cite this

Watkins, Harriet A. ; Rathbone, Dan L. ; Barwell, James ; Hay, Debbie L. ; Poyner, David R. / Structure-activity relationships for α-calcitonin gene-related peptide. In: British Journal of Pharmacology. 2013 ; Vol. 170, No. 7. pp. 1308-1322.
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Structure-activity relationships for α-calcitonin gene-related peptide. / Watkins, Harriet A.; Rathbone, Dan L.; Barwell, James; Hay, Debbie L.; Poyner, David R.

In: British Journal of Pharmacology, Vol. 170, No. 7, 12.2013, p. 1308-1322.

Research output: Contribution to journalArticle

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