Dynamics of the Apo µ-Opioid Receptor in Complex with Gi Protein.
G protein signaling
Guanosine Di-phosphate (GDP)
molecular dynamics
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Aug 2023
30 Aug 2023
Historique:
received:
01
07
2023
revised:
24
08
2023
accepted:
25
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
epublish
Résumé
Opioid receptors, particularly the µ-opioid receptor (μOR), play a pivotal role in mediating the analgesic and addictive effects of opioid drugs. G protein signaling is an important pathway of μOR function, usually associated with painkilling effects. However, the molecular mechanisms underlying the interaction between the μOR and G protein remain poorly understood. In this study, we employed classical all-atom molecular dynamics simulations to investigate the structural changes occurring with the μOR-G protein complex under two different conditions: with the G protein in the apo form (open) and with the GDP bound G protein (closed, holo form). The receptor was in the apo form and active conformation in both cases, and the simulation time comprised 1µs for each system. In order to assess the effect of the G protein coupling on the receptor activation state, three parameters were monitored: the correlation of the distance between TM3 and TM6 and the RMSD of the NPxxYA motif; the universal activation index (A100); and the χ
Identifiants
pubmed: 37686252
pii: ijms241713430
doi: 10.3390/ijms241713430
pmc: PMC10487971
pii:
doi:
Substances chimiques
Analgesics, Opioid
0
Receptors, Opioid
0
GTP-Binding Protein alpha Subunits, Gi-Go
EC 3.6.5.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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