View source for 9oup


==Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alpha6-gamma2 subtype, in complex with GABA==
<StructureSection load='9oup' size='340' side='right'caption='[[9oup]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9oup]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9OUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OUP 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]] 2.82&#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=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=9oup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9oup OCA], [https://pdbe.org/9oup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9oup RCSB], [https://www.ebi.ac.uk/pdbsum/9oup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9oup ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
GABA(A) receptors (GABA(A)Rs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although alpha1-containing GABA(A)Rs are broadly expressed and are pharmacologically important, the molecular diversity of native alpha1-based assemblies in specific brain regions remains incompletely understood. Here, we use immunofluorescence, mass spectrometry, and cryogenic electron microscopy (cryo-EM) to characterize the spatial distribution, subunit composition, and structural architecture of native alpha1-containing GABA(A)Rs in the rat cerebellum. Confocal microscopy reveals robust colocalization of alpha1 and gamma2 subunits across cerebellar layers, including prominent labeling at glomerular synapses. Biochemical purification and proteomic analysis identify a range of alpha, beta, and gamma subunits, along with abundant alpha6 and delta subunits. Using cryo-EM and automated subunit identification, we resolve eight alpha1-containing receptor assemblies, including the first structure of alpha6-containing receptors. We further determine the binding mode of the alpha6-selective pyrazoloquinolinone modulator PZ-II-029 at the alpha(+)/gamma(-) interface, showing ligand-induced expansion of the entire extracellular domain (ECD). Together, our study defines the structure and subunit composition of the alpha1-containing cerebellar GABA(A)Rs and elaborates the molecular interactions between native receptors and pyrazoloquinolinone, thereby laying the groundwork for brain region and subunit-specific pharmacology.

Molecular assemblies and pharmacology of cerebellar GABA(A) receptors.,Sun C, Jahncke JN, Wright KM, Gouaux E Proc Natl Acad Sci U S A. 2026 Feb 10;123(6):e2524504123. doi: , 10.1073/pnas.2524504123. Epub 2026 Feb 6. PMID:41650215<ref>PMID:41650215</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Gouaux E]]
[[Category: Sun C]]