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

Conner, A.C.; Simms, J.; Hay, D.L.; Mahmoud, K.; Howitt, S.G.; Wheatley, M. and Poyner, D.R. (2004). Heterodimers and family-B GPCRs:RAMPs, CGRP and adrenomedullin. Biochemical Society Transactions, 32 (5), pp. 843-846.

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 DOI: https://doi.org/10.1042/BST0320843
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences > Pharmacy
Additional Information: Bioscience 2004 Conference, Glasgow (UK), 18-22 July 2004.
Uncontrolled Keywords: adrenomedullin,calcitonin gene-related peptide,CGRP,calcitonin receptor-like receptor,receptor activity-modifying protein 1,RAMP1,RAMP2,RAMP3,Biochemistry
Published Date: 2004

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