Structure and dynamics of the CGRP receptor in apo and peptide-bound forms.
Animals
Apoproteins
/ chemistry
Calcitonin Gene-Related Peptide
/ chemistry
Calcitonin Receptor-Like Protein
/ chemistry
Cell Line
Cell Membrane
/ metabolism
Cryoelectron Microscopy
GTP-Binding Protein alpha Subunits, Gs
/ chemistry
Humans
Hydrogen Deuterium Exchange-Mass Spectrometry
Ligands
Models, Molecular
Moths
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Protein Structure, Secondary
Receptor Activity-Modifying Protein 1
/ chemistry
Receptors, Calcitonin Gene-Related Peptide
/ chemistry
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
09 04 2021
09 04 2021
Historique:
received:
15
11
2020
accepted:
11
02
2021
pubmed:
20
2
2021
medline:
28
4
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
G protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only a limited understanding of the behavior of GPCRs in the apo state and the conformational changes upon agonist binding that lead to G protein recruitment and activation. We expressed and purified unmodified apo and peptide-bound calcitonin gene-related peptide (CGRP) receptors from insect cells to determine their cryo-electron microscopy (cryo-EM) structures, and we complemented these with analysis of protein conformational dynamics using hydrogen-deuterium exchange mass spectrometry and three-dimensional variance analysis of the cryo-EM data. Together with our previously published structure of the active, Gs-bound CGRP receptor complex, our work provides insight into the mechanisms of class B1 GPCR activation.
Identifiants
pubmed: 33602864
pii: science.abf7258
doi: 10.1126/science.abf7258
pii:
doi:
Substances chimiques
Apoproteins
0
CALCRL protein, human
0
Calcitonin Receptor-Like Protein
0
Ligands
0
RAMP1 protein, human
0
Receptor Activity-Modifying Protein 1
0
Receptors, Calcitonin Gene-Related Peptide
0
GTP-Binding Protein alpha Subunits, Gs
EC 3.6.5.1
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.