|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation B== | | ==Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation B== |
| - | <SX load='6d6t' size='340' side='right' viewer='molstar' caption='[[6d6t]], [[Resolution|resolution]] 3.80Å' scene=''> | + | <SX load='6d6t' size='340' side='right' viewer='molstar' caption='[[6d6t]], [[Resolution|resolution]] 3.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d6t]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D6T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D6T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d6t]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D6T 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=FYP:ethyl+8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate'>FYP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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]] 3.86Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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=FYP:ethyl+8-fluoranyl-5-methyl-6-oxidanylidene-4~{H}-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate'>FYP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GABRB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GABRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GABRG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6d6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d6t OCA], [https://pdbe.org/6d6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d6t RCSB], [https://www.ebi.ac.uk/pdbsum/6d6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d6t 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=6d6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d6t OCA], [http://pdbe.org/6d6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d6t RCSB], [http://www.ebi.ac.uk/pdbsum/6d6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d6t ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN]] Juvenile myoclonic epilepsy;Childhood absence epilepsy;Dravet syndrome. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN] Juvenile myoclonic epilepsy;Childhood absence epilepsy;Dravet syndrome. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GBRB2_HUMAN GBRB2_HUMAN]] 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:19763268</ref> <ref>PMID:8264558</ref> [[http://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN]] 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 (By similarity). | + | [https://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN] 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 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 29: |
Line 28: |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Hibbs, R E]] | + | [[Category: Hibbs RE]] |
| - | [[Category: Jr, R M.Walsh]]
| + | [[Category: Kim JJ]] |
| - | [[Category: Kim, J J]] | + | [[Category: Noviello CM]] |
| - | [[Category: Noviello, C M]] | + | [[Category: Teng J]] |
| - | [[Category: Teng, J]] | + | [[Category: Walsh Jr RM]] |
| - | [[Category: Zhu, S]] | + | [[Category: Zhu S]] |
| - | [[Category: Cys-loop receptor]] | + | |
| - | [[Category: Gaba-a receptor]]
| + | |
| - | [[Category: Ligand-gated ion channel]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
GBRA1_HUMAN Juvenile myoclonic epilepsy;Childhood absence epilepsy;Dravet syndrome. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
GBRA1_HUMAN 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 (By similarity).
Publication Abstract from PubMed
Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (gamma-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human alpha1beta2gamma2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.
Structure of a human synaptic GABAA receptor.,Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun, 27. PMID:29950725[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE. Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun, 27. PMID:29950725 doi:http://dx.doi.org/10.1038/s41586-018-0255-3
|
