Heterodimers and Family B GPCRs, CGRP and adrenomedullin

Research output: Contribution to journalArticle

Authors

  • JH Simms
  • DL Hay
  • K Mahmoud
  • DR Poyner

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)843-846
Number of pages4
JournalBiochemical Society Transactions
Volume32
Publication statusPublished - 1 Jan 2004

Keywords

  • calcitonin receptor-like receptor, RAMP3, calcitonin gene-related peptide (CGRP), RAMP2, receptor activity-modifying protein 1 (RAMP1), adrenomedullin