View source for 6nzz


==LRRC8A-DCPIB in MSP1E3D1 nanodisc expanded state==
<SX load='6nzz' size='340' side='right' viewer='molstar' caption='[[6nzz]], [[Resolution|resolution]] 3.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nzz]] is a 6 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=6NZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NZZ 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]] 3.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L9Y:4-[[(2~{S})-2-butyl-6,7-bis(chloranyl)-2-cyclopentyl-1-oxidanylidene-3~{H}-inden-5-yl]oxy]butanoic+acid'>L9Y</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=6nzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzz OCA], [https://pdbe.org/6nzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nzz RCSB], [https://www.ebi.ac.uk/pdbsum/6nzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzz ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/LRC8A_MOUSE LRC8A_MOUSE] Essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and may also conduct organic osmolytes like taurine. Required for channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. Can form functional channels by itself (in vitro) (By similarity). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746, PubMed:24752297). Also required for T-cell development (PubMed:24752297).[UniProtKB:Q8IWT6]<ref>PMID:14660746</ref> <ref>PMID:24752297</ref> 
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== Publication Abstract from PubMed ==
Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of Mus musculus LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs.,Kern DM, Oh S, Hite RK, Brohawn SG Elife. 2019 Feb 18;8. pii: 42636. doi: 10.7554/eLife.42636. PMID:30775971<ref>PMID:30775971</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 6nzz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Brohawn SG]]
[[Category: Hite RK]]
[[Category: Kern DM]]