View source for 5osc


==GLIC-GABAAR alpha1 chimera crystallized in complex with pregnenolone sulfate at pH 4.5==
<StructureSection load='5osc' size='340' side='right'caption='[[5osc]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5osc]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Gloeobacter_violaceus_PCC_7421 Gloeobacter violaceus PCC 7421] 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=5OSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OSC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A8W:Pregnenolone+sulfate'>A8W</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=5osc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osc OCA], [https://pdbe.org/5osc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5osc RCSB], [https://www.ebi.ac.uk/pdbsum/5osc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5osc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBRA1_MOUSE GBRA1_MOUSE] Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:27129275). GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).[UniProtKB:P62813]<ref>PMID:25348603</ref> <ref>PMID:27129275</ref> [https://www.uniprot.org/uniprot/GLIC_GLOVI GLIC_GLOVI] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.<ref>PMID:17167423</ref> [https://www.uniprot.org/uniprot/GBRA2_MOUSE GBRA2_MOUSE] Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha2/beta2/gamma2 receptor exhibits synaptogenic activity whereas the alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (PubMed:27129275).<ref>PMID:27129275</ref> 
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== Publication Abstract from PubMed ==
gamma-Aminobutyric acid receptors (GABAARs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABAARs is the alpha subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABAAR function requires high-resolution structures. Here we present the first atomic structures of a GABAAR chimera at 2.8-A resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the alpha-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABAARs in neurological disorders.

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.,Laverty D, Thomas P, Field M, Andersen OJ, Gold MG, Biggin PC, Gielen M, Smart TG Nat Struct Mol Biol. 2017 Oct 2. doi: 10.1038/nsmb.3477. PMID:28967882<ref>PMID:28967882</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5osc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gloeobacter violaceus PCC 7421]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Gold MG]]
[[Category: Laverty DC]]
[[Category: Smart TG]]