4or2
From Proteopedia
Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator
Structural highlights
DiseaseGRM1_HUMAN Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency. The disease is caused by mutations affecting the gene represented in this entry.[1] FunctionC562_ECOLX Electron-transport protein of unknown function.GRM1_HUMAN G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum.[2] Publication Abstract from PubMedThe excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.,Wu H, Wang C, Gregory KJ, Han GW, Cho HP, Xia Y, Niswender CM, Katritch V, Meiler J, Cherezov V, Conn PJ, Stevens RC Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar , 6. PMID:24603153[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Escherichia coli | Homo sapiens | Large Structures | Cherezov V | Cho HP | Conn PJ | Gregory KJ | Han GW | Katritch V | Niswender CM | Stevens RC | Wang C | Wu H | Xia Y
