Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin

Biochem Soc Trans. 2004 Nov;32(Pt 5):843-6. doi: 10.1042/BST0320843.

Abstract

RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, allowing the generation of six distinct receptors with preferences for CGRP (CT gene-related peptide), adrenomedullin, amylin and CT. There are three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of receptor pharmacology, whereas the transmembrane domain contributes to association of the RAMP with the GPCR. The N-terminus of all members of the RAMP family probably contains two disulphide bonds; a potential third disulphide is found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the ligand and plays a key role in its binding, either directly or indirectly. BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very high selectivity for the human CGRP(1) receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenomedullin
  • Amino Acid Sequence
  • Animals
  • Calcitonin Gene-Related Peptide / chemistry
  • Dimerization
  • Glycosylation
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Ligands
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / physiology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptor Activity-Modifying Protein 1
  • Receptor Activity-Modifying Protein 3
  • Receptor Activity-Modifying Proteins
  • Receptors, Calcitonin / chemistry*
  • Receptors, Calcitonin Gene-Related Peptide / chemistry
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / physiology*
  • Sequence Homology, Amino Acid

Substances

  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Peptides
  • RAMP1 protein, human
  • RAMP3 protein, human
  • Receptor Activity-Modifying Protein 1
  • Receptor Activity-Modifying Protein 3
  • Receptor Activity-Modifying Proteins
  • Receptors, Calcitonin
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, G-Protein-Coupled
  • Adrenomedullin
  • Calcitonin Gene-Related Peptide