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.
Originalsprog | Engelsk |
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Tidsskrift | Nature |
Vol/bind | 566 |
Udgave nummer | 7742 |
Sider (fra-til) | 79-84 |
ISSN | 0028-0836 |
DOI | |
Status | Udgivet - 7 feb. 2019 |
Bibliografisk note
Correction to: Nature https://doi.org/10.1038/s41586-019-0881-4, published online 23 January 2019.In the author list of the original Article, the surname of author Toon Laeremans was misspelled ‘Laermans’. The original Article has been corrected online.