Mutations in the NPxxY motif stabilize pharmacologically distinct conformational states of the α


Journal

Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400

Informations de publication

Date de publication:
12 03 2019
Historique:
entrez: 14 3 2019
pubmed: 14 3 2019
medline: 15 5 2020
Statut: epublish

Résumé

G protein-coupled receptors (GPCRs) convert extracellular stimuli to intracellular responses that regulate numerous physiological processes. Crystallographic and biophysical advances in GPCR structural analysis have aided investigations of structure-function relationships that clarify our understanding of these dynamic receptors, but the molecular mechanisms associated with activation and signaling for individual GPCRs may be more complex than was previously appreciated. Here, we investigated the proposed water-mediated, hydrogen-bonded activation switch between the conserved NPxxY motif on transmembrane helix 7 (TMH7) and a conserved tyrosine in TMH5, which contributes to α

Identifiants

pubmed: 30862702
pii: 12/572/eaas9485
doi: 10.1126/scisignal.aas9485
pii:
doi:

Substances chimiques

Receptors, Adrenergic, alpha-1 0
Receptors, Adrenergic, beta-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Auteurs

Lotten Ragnarsson (L)

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. l.ragnarsson@imb.uq.edu.au r.lewis@imb.uq.edu.au.

Åsa Andersson (Å)

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.

Walter G Thomas (WG)

School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.

Richard J Lewis (RJ)

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. l.ragnarsson@imb.uq.edu.au r.lewis@imb.uq.edu.au.

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Classifications MeSH