6N4X

Metabotropic Glutamate Receptor 5 Apo Form Ligand Binding Domain

6N4X の概要

• エントリーDOI: 10.2210/pdb6n4x/pdb
• 分子名称: Metabotropic glutamate receptor 5, 2-acetamido-2-deoxy-beta-D-glucopyranose, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: cell surface receptor, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 198365.24

構造登録者

Koehl, A.,Hu, H.,Feng, D.,Sun, B.,Weis, W.I.,Skiniotis, G.S.,Mathiesen, J.M.,Kobilka, B.K. (登録日: 2018-11-20, 公開日: 2019-01-23, 最終更新日: 2023-10-11)

主引用文献

Koehl, A.,Hu, H.,Feng, D.,Sun, B.,Zhang, Y.,Robertson, M.J.,Chu, M.,Kobilka, T.S.,Laermans, T.,Steyaert, J.,Tarrasch, J.,Dutta, S.,Fonseca, R.,Weis, W.I.,Mathiesen, J.M.,Skiniotis, G.,Kobilka, B.K.
Structural insights into the activation of metabotropic glutamate receptors.
Nature, 566:79-84, 2019

PubMed Abstract: Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling.

PubMed: 30675062
DOI: 10.1038/s41586-019-0881-4

実験手法

X-RAY DIFFRACTION (4 Å)