8t6j
From Proteopedia
CDPPB-bound inactive mGlu5
Structural highlights
FunctionGRM5_HUMAN Receptor for glutamate. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Publication Abstract from PubMedMetabotropic 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
