View source for 7pbd


==a1b3 GABA-A receptor + GABA==
<StructureSection load='7pbd' size='340' side='right'caption='[[7pbd]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pbd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PBD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.04&#8491;</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=HSM:HISTAMINE'>HSM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7pbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pbd OCA], [https://pdbe.org/7pbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pbd RCSB], [https://www.ebi.ac.uk/pdbsum/7pbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pbd ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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;">
== Publication Abstract from PubMed ==
Type A GABA (gamma-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of alpha-, beta-, gamma-, delta-, epsilon-, rho-, theta- and pi-subunits(1). alphabeta, alpha4betadelta, alpha6betadelta and alpha5betagamma receptors favour extrasynaptic localization, and mediate an essential persistent (tonic) inhibitory conductance in many regions of the mammalian brain(1,2). Mutations of these receptors in humans are linked to epilepsy and insomnia(3,4). Altered extrasynaptic receptor function is implicated in insomnia, stroke and Angelman and Fragile X syndromes(1,5), and drugs targeting these receptors are used to treat postpartum depression(6). Tonic GABAergic responses are moderated to avoid excessive suppression of neuronal communication, and can exhibit high sensitivity to Zn(2+) blockade, in contrast to synapse-preferring alpha1betagamma, alpha2betagamma and alpha3betagamma receptor responses(5,7-12). Here, to resolve these distinctive features, we determined structures of the predominantly extrasynaptic alphabeta GABA(A) receptor class. An inhibited state bound by both the lethal paralysing agent alpha-cobratoxin(13) and Zn(2+) was used in comparisons with GABA-Zn(2+) and GABA-bound structures. Zn(2+) nullifies the GABA response by non-competitively plugging the extracellular end of the pore to block chloride conductance. In the absence of Zn(2+), the GABA signalling response initially follows the canonical route until it reaches the pore. In contrast to synaptic GABA(A) receptors, expansion of the midway pore activation gate is limited and it remains closed, reflecting the intrinsic low efficacy that characterizes the extrasynaptic receptor. Overall, this study explains distinct traits adopted by alphabeta receptors that adapt them to a role in tonic signalling.

Mechanisms of inhibition and activation of extrasynaptic alphabeta GABA(A) receptors.,Kasaragod VB, Mortensen M, Hardwick SW, Wahid AA, Dorovykh V, Chirgadze DY, Smart TG, Miller PS Nature. 2022 Feb;602(7897):529-533. doi: 10.1038/s41586-022-04402-z. Epub 2022 , Feb 9. PMID:35140402<ref>PMID:35140402</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pbd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Kasaragod VB]]
[[Category: Miller PS]]