7EPE

Crystal structure of mGlu2 bound to NAM563

7EPE の概要

• エントリーDOI: 10.2210/pdb7epe/pdb
• 分子名称: Metabotropic glutamate receptor 2, FLAVIN MONONUCLEOTIDE, 4-(1-methylpyrazol-4-yl)-7-[[(2~{S})-2-(trifluoromethyl)morpholin-4-yl]methyl]quinoline-2-carboxamide (3 entities in total)
• 機能のキーワード: membrane protein, gpcr
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49372.32

構造登録者

Du, J.,Wang, D.,Lin, S.,Han, S.,Wu, B.,Zhao, Q. (登録日: 2021-04-26, 公開日: 2021-06-23, 最終更新日: 2024-10-30)

主引用文献

Du, J.,Wang, D.,Fan, H.,Xu, C.,Tai, L.,Lin, S.,Han, S.,Tan, Q.,Wang, X.,Xu, T.,Zhang, H.,Chu, X.,Yi, C.,Liu, P.,Wang, X.,Zhou, Y.,Pin, J.P.,Rondard, P.,Liu, H.,Liu, J.,Sun, F.,Wu, B.,Zhao, Q.
Structures of human mGlu2 and mGlu7 homo- and heterodimers.
Nature, 594:589-593, 2021

PubMed Abstract: The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties. 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.

PubMed: 34135509
DOI: 10.1038/s41586-021-03641-w

実験手法

X-RAY DIFFRACTION (2.5 Å)