Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin
Animals
Humans
Adrenomedullin
/ chemistry
Calcitonin Gene-Related Peptide
/ metabolism
Calcitonin Receptor-Like Protein
/ genetics
Chlorocebus aethiops
COS Cells
Cyclic AMP
/ metabolism
HEK293 Cells
Models, Molecular
Molecular Dynamics Simulation
Protein Stability
Receptor Activity-Modifying Proteins
/ chemistry
Receptors, Adrenomedullin
/ genetics
Receptors, G-Protein-Coupled
/ genetics
Signal Transduction
Bioluminescence resonance energy transfer (BRET)
G protein–coupled receptor (GPCR)
kinetic selectivity
long residence time agonist
molecular dynamics
molecular pharmacology
peptide hormone
receptor structure–function
signaling
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
31
01
2023
revised:
20
04
2023
accepted:
01
05
2023
medline:
28
6
2023
pubmed:
6
5
2023
entrez:
5
5
2023
Statut:
ppublish
Résumé
Adrenomedullin 2/intermedin (AM2/IMD), adrenomedullin (AM), and calcitonin gene-related peptide (CGRP) have functions in the cardiovascular, lymphatic, and nervous systems by activating three heterodimeric receptors comprising the class B GPCR CLR and a RAMP1, -2, or -3 modulatory subunit. CGRP and AM prefer the RAMP1 and RAMP2/3 complexes, respectively, whereas AM2/IMD is thought to be relatively nonselective. Accordingly, AM2/IMD exhibits overlapping actions with CGRP and AM, so the rationale for this third agonist for the CLR-RAMP complexes is unclear. Here, we report that AM2/IMD is kinetically selective for CLR-RAMP3, known as the AM
Identifiants
pubmed: 37146967
pii: S0021-9258(23)01813-6
doi: 10.1016/j.jbc.2023.104785
pmc: PMC10248883
pii:
doi:
Substances chimiques
Adrenomedullin
148498-78-6
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Calcitonin Receptor-Like Protein
0
Cyclic AMP
E0399OZS9N
Receptor Activity-Modifying Proteins
0
Receptors, Adrenomedullin
0
Receptors, G-Protein-Coupled
0
ADM2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
104785Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM104251
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130794
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest K. M. B. and A. A. P. are filing a patent on kinetically selective AM and AM2/IMD variants.