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-Structure paper
Title | Structural insights into the activation of metabotropic glutamate receptors. |
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Journal, issue, pages | Nature, Vol. 566, Issue 7742, Page 79-84, Year 2019 |
Publish date | Jan 23, 2019 |
Authors | 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 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 ...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. |
External links | Nature / PubMed:30675062 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 3.262 - 7.9 Å |
Structure data | EMDB-0345, PDB-6n51: EMDB-0346, PDB-6n52: EMDB-0347: PDB-6n4x: PDB-6n4y: PDB-6n50: |
Chemicals | ChemComp-NAG: ChemComp-MG: ChemComp-QUS: |
Source |
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Keywords | MEMBRANE PROTEIN / Cell Surface Receptor / Cell Surface Receptor Nanobody / SIGNALING PROTEIN |