Structures of human mGlu2 and mGlu7 homo- and heterodimers - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Année : 2021

Structures of human mGlu2 and mGlu7 homo- and heterodimers

Juan Du
Jean-Philippe Pin
Philippe Rondard
  • Fonction : Auteur
  • PersonId : 853446
Qiang Zhao
  • Fonction : Auteur correspondant
  • PersonId : 1103105

Connectez-vous pour contacter l'auteur

Résumé

The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system1. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties2-4. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation.
Fichier principal
Vignette du fichier
Du mGlu2-7 Nature 2021.pdf (5.19 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03269110 , version 1 (17-11-2021)

Identifiants

Citer

Juan Du, Dejian Wang, Hongcheng Fan, Chanjuan Xu, Linhua Tai, et al.. Structures of human mGlu2 and mGlu7 homo- and heterodimers. Nature, 2021, 594 (7864), pp.589-593. ⟨10.1038/s41586-021-03641-w⟩. ⟨hal-03269110⟩
55 Consultations
617 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More