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-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 |
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キーワード | MEMBRANE PROTEIN / Cell Surface Receptor / Cell Surface Receptor Nanobody / SIGNALING PROTEIN |
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