RAMPs as allosteric modulators of the calcitonin and calcitonin-like class B G protein-coupled receptors.
Allostery
Class B GPCR
Dynamics
Peptide hormone
RAMP
Journal
Advances in pharmacology (San Diego, Calif.)
ISSN: 1557-8925
Titre abrégé: Adv Pharmacol
Pays: United States
ID NLM: 9015397
Informations de publication
Date de publication:
2020
2020
Historique:
entrez:
18
5
2020
pubmed:
18
5
2020
medline:
30
9
2020
Statut:
ppublish
Résumé
Receptor activity-modifying proteins (RAMPs) are a family of three single span transmembrane proteins in humans that interact with many GPCRs and can modulate their function. RAMPs were discovered as key components of the calcitonin gene-related peptide and adrenomedullin receptors. They are required for transport of this class B GPCR, calcitonin receptor-like receptor (CLR), to the cell surface and determine its peptide ligand binding preferences. Soon thereafter RAMPs were shown to modulate the binding of calcitonin and amylin peptides to the related calcitonin receptor (CTR) and in the years since an ever-growing number of RAMP-interacting receptors have been identified including most if not all of the 15 class B GPCRs and several GPCRs from other families. Studies of CLR, CTR, and a handful of other GPCRs revealed that RAMPs are able to modulate various aspects of receptor function including trafficking, ligand binding, and signaling. Here, we review RAMP interactions and functions with an emphasis on class B receptors for which our understanding is most advanced. A key focus is to discuss recent evidence that RAMPs serve as endogenous allosteric modulators of CLR and CTR. We discuss structural studies of RAMP-CLR complexes and CTR and biochemical and pharmacological studies that collectively have significantly expanded our understanding of the mechanistic basis for RAMP modulation of these class B GPCRs. Last, we consider the implications of these findings for drug development targeting RAMP-CLR/CTR complexes.
Identifiants
pubmed: 32416865
pii: S1054-3589(20)30001-6
doi: 10.1016/bs.apha.2020.01.001
pmc: PMC7374980
mid: NIHMS1609867
pii:
doi:
Substances chimiques
Calcitonin Receptor-Like Protein
0
Ligands
0
Receptor Activity-Modifying Proteins
0
Receptors, Calcitonin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
115-141Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM104251
Pays : United States
Informations de copyright
© 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest A.A.P. is inventor on a patent describing enhanced affinity and altered selectivity AM and CGRP variant peptides.
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