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==Crystal structure of a | |||
<StructureSection load='4cof' size='340' side='right' caption='[[4cof]], [[Resolution|resolution]] 2.97Å' scene=''> | ==Crystal structure of a human gamma-aminobutyric acid receptor, the GABA(A)R-beta3 homopentamer== | ||
<StructureSection load='4cof' size='340' side='right'caption='[[4cof]], [[Resolution|resolution]] 2.97Å' scene=''> | |||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cof]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COF OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4cof]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4COF FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>< | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.97Å</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<table> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cof OCA], [https://pdbe.org/4cof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cof RCSB], [https://www.ebi.ac.uk/pdbsum/4cof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cof ProSAT]</span></td></tr> | ||
</table> | |||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/GBRB3_HUMAN GBRB3_HUMAN] Autism;Childhood absence epilepsy. Disease susceptibility is associated with variations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[ | [https://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. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type-A gamma-aminobutyric acid receptors (GABAARs) are the principal mediators of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy. Here we present the first three-dimensional structure of a GABAAR, the human beta3 homopentamer, at 3 A resolution. This structure reveals architectural elements unique to eukaryotic Cys-loop receptors, explains the mechanistic consequences of multiple human disease mutations and shows an unexpected structural role for a conserved N-linked glycan. The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators. The channel region forms a closed gate at the base of the pore, representative of a desensitized state. These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission. | |||
Crystal structure of a human GABA receptor.,Miller PS, Aricescu AR Nature. 2014 Jun 8. doi: 10.1038/nature13293. PMID:24909990<ref>PMID:24909990</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cof" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[GABA receptor 3D structures|GABA receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Aricescu AR]] | ||
[[Category: Miller PS]] | |||