Structural insights into µ-opioid receptor activation

Abstract : Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β2-adrenergic receptor (β2AR) and the M2 muscarinic receptor. Comparison with active β2AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.umontpellier.fr/hal-02067966
Contributeur : Mélanie Karli <>
Soumis le : jeudi 14 mars 2019 - 14:58:37
Dernière modification le : mardi 20 août 2019 - 18:14:02

Lien texte intégral

Identifiants

Collections

Citation

Weijiao Huang, Aashish Manglik, A. Venkatakrishnan, Toon Laeremans, Evan Feinberg, et al.. Structural insights into µ-opioid receptor activation. Nature, Nature Publishing Group, 2015, 524 (7565), pp.315-321. ⟨10.1038/nature14886⟩. ⟨hal-02067966⟩

Partager

Métriques

Consultations de la notice

21