8foi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:37, 17 October 2024) (edit) (undo)
 
Line 5: Line 5:
<table><tr><td colspan='2'>[[8foi]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FOI FirstGlance]. <br>
<table><tr><td colspan='2'>[[8foi]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FOI 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]] 2.5&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.5&#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=D12:DODECANE'>D12</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y4B:allopregnanolone'>Y4B</scene></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=D12:DODECANE'>D12</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y4B:1-[(3~{R},5~{S},8~{R},9~{S},10~{S},13~{S},14~{S},17~{S})-10,13-dimethyl-3-oxidanyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]ethanone'>Y4B</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=8foi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8foi OCA], [https://pdbe.org/8foi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8foi RCSB], [https://www.ebi.ac.uk/pdbsum/8foi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8foi ProSAT]</span></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=8foi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8foi OCA], [https://pdbe.org/8foi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8foi RCSB], [https://www.ebi.ac.uk/pdbsum/8foi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8foi ProSAT]</span></td></tr>
</table>
</table>
-
== Function ==
+
<div style="background-color:#fffaf0;">
-
[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>
+
== Publication Abstract from PubMed ==
 +
Type A gamma-aminobutyric acid receptors (GABA(A)Rs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants(1-3). However, our understanding of GABA(A)R pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits(4) and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABA(A)R assemblies containing the widely expressed alpha1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron microscopy (cryo-EM) analysis and single-molecule photobleaching experiments, we uncover three major structural populations in the brain: the canonical alpha1beta2gamma2 receptor containing two alpha1 subunits, and two assemblies containing one alpha1 and either an alpha2 or alpha3 subunit, in which the single alpha1-containing receptors feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, APG is bound at the transmembrane alpha/beta subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABA(A)Rs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify the ion channel pore and the binding sites for GABA and insomnia medications. Our data reveal the major alpha1-containing GABA(A)R assemblies, bound with endogenous neurosteroid, thus defining a structural landscape from which subtype-specific drugs can be developed.
 +
 
 +
Cryo-EM structures reveal native GABA(A) receptor assemblies and pharmacology.,Sun C, Zhu H, Clark S, Gouaux E Nature. 2023 Oct;622(7981):195-201. doi: 10.1038/s41586-023-06556-w. Epub 2023 , Sep 20. PMID:37730991<ref>PMID:37730991</ref>
 +
 
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 8foi" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Current revision

Native GABA-A receptor from the mouse brain, alpha1-beta2-gamma2 subtype, in complex with GABA and allopregnanolone

PDB ID 8foi

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8foi"
Personal tools