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== Publication Abstract from PubMed ==

Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging we reveal distinct receptor conformations upon allosteric modulator and G protein binding.

Step-wise activation of a Family C GPCR.,Kumar KK, Wang H, Habrian C, Latorraca NR, Xu J, O'Brien ES, Zhang C, Montabana E, Koehl A, Marqusee S, Isacoff EY, Kobilka BK bioRxiv. 2023 Aug 30:2023.08.29.555158. doi: 10.1101/2023.08.29.555158. Preprint. PMID:37693614<ref>PMID:37693614</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

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