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8t7h

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Current revision (19:57, 29 May 2024) (edit) (undo)
 
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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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.
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Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain(1). Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain(2). 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.
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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>
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Stepwise activation of a metabotropic glutamate receptor.,Krishna Kumar K, Wang H, Habrian C, Latorraca NR, Xu J, O'Brien ES, Zhang C, Montabana E, Koehl A, Marqusee S, Isacoff EY, Kobilka BK Nature. 2024 May;629(8013):951-956. doi: 10.1038/s41586-024-07327-x. Epub 2024 , Apr 17. PMID:38632403<ref>PMID:38632403</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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Quis-bound intermediate mGlu5

PDB ID 8t7h

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