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.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Conner AC,Simms J,Hay DL,Mahmoud K,Howitt SG,Wheatley M,Poyner DRdoi
10.1042/BST0320843keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
843-6issue
Pt 5eissn
0300-5127issn
1470-8752pii
BST0320843journal_volume
32pub_type
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