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| | <SX load='6dw1' size='340' side='right' viewer='molstar' caption='[[6dw1]], [[Resolution|resolution]] 3.10Å' scene=''> | | <SX load='6dw1' size='340' side='right' viewer='molstar' caption='[[6dw1]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dw1]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DW1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DW1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dw1]] is a 5 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=6DW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DW1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6dw0|6dw0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gabrg2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Gabra1, Gabra-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Gabrb1, Gabrb-1 ([http://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=6dw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dw1 OCA], [https://pdbe.org/6dw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dw1 RCSB], [https://www.ebi.ac.uk/pdbsum/6dw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dw1 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6dw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dw1 OCA], [http://pdbe.org/6dw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dw1 RCSB], [http://www.ebi.ac.uk/pdbsum/6dw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dw1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GBRG2_RAT GBRG2_RAT]] GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. [[http://www.uniprot.org/uniprot/GBRB1_RAT GBRB1_RAT]] Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.<ref>PMID:18281286</ref> <ref>PMID:1977069</ref> [[http://www.uniprot.org/uniprot/GBRA1_RAT GBRA1_RAT]] Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.<ref>PMID:1376242</ref> <ref>PMID:18281286</ref> <ref>PMID:2540033</ref> | + | [https://www.uniprot.org/uniprot/GBRG2_RAT GBRG2_RAT] GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Phulera, S]] | + | [[Category: Gouaux E]] |
| - | [[Category: Yoshioka, C]] | + | [[Category: Phulera S]] |
| - | [[Category: Yu, J]] | + | [[Category: Yoshioka C]] |
| - | [[Category: Zhu, H]] | + | [[Category: Yu J]] |
| - | [[Category: Cys loop receptor]]
| + | [[Category: Zhu H]] |
| - | [[Category: Gaba]]
| + | |
| - | [[Category: Gaba receptor]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Neurotransmission]]
| + | |
| Structural highlights
Function
GBRG2_RAT GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Publication Abstract from PubMed
Fast inhibitory neurotransmission in mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases. Despite profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of tri-heteromeric alpha1beta1gamma2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 A resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the alpha1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA.,Phulera S, Zhu H, Yu J, Claxton DP, Yoder N, Yoshioka C, Gouaux E Elife. 2018 Jul 25;7. pii: 39383. doi: 10.7554/eLife.39383. PMID:30044221[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Phulera S, Zhu H, Yu J, Claxton DP, Yoder N, Yoshioka C, Gouaux E. Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA. Elife. 2018 Jul 25;7. pii: 39383. doi: 10.7554/eLife.39383. PMID:30044221 doi:http://dx.doi.org/10.7554/eLife.39383
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