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| | <StructureSection load='3gba' size='340' side='right'caption='[[3gba]], [[Resolution|resolution]] 1.35Å' scene=''> | | <StructureSection load='3gba' size='340' side='right'caption='[[3gba]], [[Resolution|resolution]] 1.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gba]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GBA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gba]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GBA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DYH:(2R,3AR,6S,7R,7AR)-2-[(2S)-2-AMINO-2-CARBOXYETHYL]-6-HYDROXY-7-(METHYLAMINO)HEXAHYDRO-2H-FURO[3,2-B]PYRAN-2-CARBOXYLIC+ACID'>DYH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ycj|1ycj]], [[3gbb|3gbb]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DYH:(2R,3AR,6S,7R,7AR)-2-[(2S)-2-AMINO-2-CARBOXYETHYL]-6-HYDROXY-7-(METHYLAMINO)HEXAHYDRO-2H-FURO[3,2-B]PYRAN-2-CARBOXYLIC+ACID'>DYH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur5, Grik1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3gba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gba OCA], [https://pdbe.org/3gba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gba RCSB], [https://www.ebi.ac.uk/pdbsum/3gba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gba ProSAT]</span></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=3gba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gba OCA], [https://pdbe.org/3gba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gba RCSB], [https://www.ebi.ac.uk/pdbsum/3gba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gba ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT]] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref>
| + | [https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Frydenvang, K]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Gajhede, M]] | + | [[Category: Frydenvang K]] |
| - | [[Category: Kastrup, J S]] | + | [[Category: Gajhede M]] |
| - | [[Category: Naur, P]] | + | [[Category: Kastrup JS]] |
| - | [[Category: Agonist]]
| + | [[Category: Naur P]] |
| - | [[Category: Iglur5]]
| + | |
| - | [[Category: Ionotropic glutamate receptor]]
| + | |
| - | [[Category: Ligand-binding core]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
GRIK1_RAT Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The prevailing structural model for ligand activation of ionotropic glutamate receptors posits that agonist efficacy arises from the stability and magnitude of induced domain closure in the ligand-binding core structure. Here we describe an exception to the correlation between ligand efficacy and domain closure. A weakly efficacious partial agonist of very low potency for homomeric iGluR5 kainate receptors, 8,9-dideoxyneodysiherbaine (MSVIII-19), induced a fully closed iGluR5 ligand-binding core. The degree of relative domain closure, approximately 30 degrees , was similar to that we resolved with the structurally related high affinity agonist dysiherbaine and to that of l-glutamate. The pharmacological activity of MSVIII-19 was confirmed in patch clamp recordings from transfected HEK293 cells, where MSVIII-19 predominantly inhibits iGluR5-2a, with little activation apparent at a high concentration (1 mm) of MSVIII-19 (<1% of mean glutamate-evoked currents). To determine the efficacy of the ligand quantitatively, we constructed concentration-response relationships for MSVIII-19 following potentiation of steady-state currents with concanavalin A (EC(50) = 3.6 microm) and on the nondesensitizing receptor mutant iGluR5-2b(Y506C/L768C) (EC(50) = 8.1 microm). MSVIII-19 exhibited a maximum of 16% of full agonist efficacy, as measured in parallel recordings with glutamate. Molecular dynamics simulations and electrophysiological recordings confirm that the specificity of MSVIII-19 for iGluR5 is partly attributable to interdomain hydrogen bond residues Glu(441) and Ser(721) in the iGluR5-S1S2 structure. The weaker interactions of MSVIII-19 with iGluR5 compared with dysiherbaine, together with altered stability of the interdomain interaction, may be responsible for the apparent uncoupling of domain closure and channel opening in this kainate receptor subunit.
Full domain closure of the ligand-binding core of the ionotropic glutamate receptor iGluR5 induced by the high affinity agonist dysiherbaine and the functional antagonist 8,9-dideoxyneodysiherbaine.,Frydenvang K, Lash LL, Naur P, Postila PA, Pickering DS, Smith CM, Gajhede M, Sasaki M, Sakai R, Pentikainen OT, Swanson GT, Kastrup JS J Biol Chem. 2009 May 22;284(21):14219-29. Epub 2009 Mar 18. PMID:19297335[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mayer ML, Ghosal A, Dolman NP, Jane DE. Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. J Neurosci. 2006 Mar 15;26(11):2852-61. PMID:16540562 doi:26/11/2852
- ↑ Frydenvang K, Lash LL, Naur P, Postila PA, Pickering DS, Smith CM, Gajhede M, Sasaki M, Sakai R, Pentikainen OT, Swanson GT, Kastrup JS. Full domain closure of the ligand-binding core of the ionotropic glutamate receptor iGluR5 induced by the high affinity agonist dysiherbaine and the functional antagonist 8,9-dideoxyneodysiherbaine. J Biol Chem. 2009 May 22;284(21):14219-29. Epub 2009 Mar 18. PMID:19297335 doi:10.1074/jbc.M808547200
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