Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.
Journal
Pharmacological reviews
ISSN: 1521-0081
Titre abrégé: Pharmacol Rev
Pays: United States
ID NLM: 0421737
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
09
08
2020
accepted:
27
09
2022
entrez:
9
2
2023
pubmed:
10
2
2023
medline:
14
2
2023
Statut:
ppublish
Résumé
G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR-RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR-RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR-RAMP-ligand complexes, and drugs have been developed that target GPCR-RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR-RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR-RAMP interactions based on a review of the current literature. SIGNIFICANCE STATEMENT: Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein-protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.
Identifiants
pubmed: 36757898
pii: pharmrev.120.000180
doi: 10.1124/pharmrev.120.000180
pmc: PMC9832379
doi:
Substances chimiques
Receptor Activity-Modifying Proteins
0
Ligands
0
Receptors, G-Protein-Coupled
0
Membrane Proteins
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-34Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM136640
Pays : United States
Informations de copyright
Copyright © 2023 by The Author(s).
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