+検索条件
-Structure paper
タイトル | Structural insights into the activation of metabotropic glutamate receptors. |
---|---|
ジャーナル・号・ページ | Nature, Vol. 566, Issue 7742, Page 79-84, Year 2019 |
掲載日 | 2019年1月23日 |
著者 | Antoine Koehl / Hongli Hu / Dan Feng / Bingfa Sun / Yan Zhang / Michael J Robertson / Matthew Chu / Tong Sun Kobilka / Toon Laeremans / Jan Steyaert / Jeffrey Tarrasch / Somnath Dutta / Rasmus Fonseca / William I Weis / Jesper M Mathiesen / Georgios Skiniotis / Brian K Kobilka / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:30675062 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.262 - 7.9 Å |
構造データ | EMDB-0345, PDB-6n51: EMDB-0347: PDB-6n4x: PDB-6n4y: PDB-6n50: |
化合物 | ChemComp-NAG: ChemComp-MG: ChemComp-QUS: |
由来 |
|
キーワード | MEMBRANE PROTEIN (膜タンパク質) / Cell Surface Receptor (細胞表面受容体) / Cell Surface Receptor Nanobody / SIGNALING PROTEIN |