6huj

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<StructureSection load='6huj' size='340' side='right' caption='[[6huj]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
<StructureSection load='6huj' size='340' side='right' caption='[[6huj]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6huj]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HUJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HUJ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6huj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HUJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HUJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene>, <scene name='pdbligand=RI5:(1AR,2AR,3S,6R,6AS,8AS,8BR,9R)-2A-HYDROXY-8B-METHYL-9-(PROP-1-EN-2-YL)HEXAHYDRO-3,6-METHANO-1,5,7-TRIOXACYCLOPENTA[IJ]CYCLOPROPA[A]AZULENE-4,8(3H)-DIONE'>RI5</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene>, <scene name='pdbligand=RI5:(1AR,2AR,3S,6R,6AS,8AS,8BR,9R)-2A-HYDROXY-8B-METHYL-9-(PROP-1-EN-2-YL)HEXAHYDRO-3,6-METHANO-1,5,7-TRIOXACYCLOPENTA[IJ]CYCLOPROPA[A]AZULENE-4,8(3H)-DIONE'>RI5</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GABRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GABRB3 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6huj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6huj OCA], [http://pdbe.org/6huj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6huj RCSB], [http://www.ebi.ac.uk/pdbsum/6huj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6huj ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6huj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6huj OCA], [http://pdbe.org/6huj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6huj RCSB], [http://www.ebi.ac.uk/pdbsum/6huj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6huj ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/GBRA1_BOVIN GBRA1_BOVIN]] 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:3037384</ref> [[http://www.uniprot.org/uniprot/GBRG2_HUMAN GBRG2_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:2538761</ref> [[http://www.uniprot.org/uniprot/GBRB3_HUMAN GBRB3_HUMAN]] 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/GBRA1_BOVIN GBRA1_BOVIN]] 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:3037384</ref> [[http://www.uniprot.org/uniprot/GBRG2_HUMAN GBRG2_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:2538761</ref> [[http://www.uniprot.org/uniprot/GBRB3_HUMAN GBRB3_HUMAN]] 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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Type-A gamma-aminobutyric (GABAA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABAA receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human alpha1beta3gamma2L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (gamma-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABAA receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABAA receptor modulators.
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GABAA receptor signalling mechanisms revealed by structural pharmacology.,Masiulis S, Desai R, Uchanski T, Serna Martin I, Laverty D, Karia D, Malinauskas T, Zivanov J, Pardon E, Kotecha A, Steyaert J, Miller KW, Aricescu AR Nature. 2019 Jan 2. pii: 10.1038/s41586-018-0832-5. doi:, 10.1038/s41586-018-0832-5. PMID:30602790<ref>PMID:30602790</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6huj" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Camelus glama]]
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[[Category: Human]]
[[Category: Aricescu, A R]]
[[Category: Aricescu, A R]]
[[Category: Desai, R]]
[[Category: Desai, R]]

Revision as of 12:38, 16 January 2019

CryoEM structure of human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex with picrotoxin, GABA and megabody Mb38.

6huj, resolution 3.04Å

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