4or2: Difference between revisions
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==Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator== | ==Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator== | ||
<StructureSection load='4or2' size='340' side='right' caption='[[4or2]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4or2' size='340' side='right'caption='[[4or2]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4or2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4or2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OR2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FM9:4-FLUORO-N-METHYL-N-{4-[6-(PROPAN-2-YLAMINO)PYRIMIDIN-4-YL]-1,3-THIAZOL-2-YL}BENZAMIDE'>FM9</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FM9:4-FLUORO-N-METHYL-N-{4-[6-(PROPAN-2-YLAMINO)PYRIMIDIN-4-YL]-1,3-THIAZOL-2-YL}BENZAMIDE'>FM9</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4or2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4or2 OCA], [https://pdbe.org/4or2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4or2 RCSB], [https://www.ebi.ac.uk/pdbsum/4or2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4or2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/GRM1_HUMAN GRM1_HUMAN] Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:22901947</ref> | |||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/GRM1_HUMAN 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.<ref>PMID:7476890</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4or2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4or2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Metabotropic glutamate receptor 3D structures|Metabotropic glutamate receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Cherezov V]] | ||
[[Category: | [[Category: Cho HP]] | ||
[[Category: Gregory | [[Category: Conn PJ]] | ||
[[Category: Han | [[Category: Gregory KJ]] | ||
[[Category: Katritch | [[Category: Han GW]] | ||
[[Category: Niswender | [[Category: Katritch V]] | ||
[[Category: Stevens | [[Category: Niswender CM]] | ||
[[Category: Wang | [[Category: Stevens RC]] | ||
[[Category: Wu | [[Category: Wang C]] | ||
[[Category: Xia | [[Category: Wu H]] | ||
[[Category: Xia Y]] | |||
Revision as of 10:41, 25 January 2023
Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulatorHuman 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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