4or2 | pdb_00004or2

Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator

spinqualitylabelsall models 4or2, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4or2 is a 2 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CLR, FM9, OLA, OLC, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GRM1_HUMAN Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function C562_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. Publication Abstract from PubMed The 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Metabotropic glutamate receptor 3D structures

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