View source for 8dra


==LRRC8A:C conformation 2 (oblong) LRR mask==
<StructureSection load='8dra' size='340' side='right'caption='[[8dra]], [[Resolution|resolution]] 3.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dra]] is a 3 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=8DRA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DRA 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]] 3.98&#8491;</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=8dra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dra OCA], [https://pdbe.org/8dra PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dra RCSB], [https://www.ebi.ac.uk/pdbsum/8dra PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dra ProSAT]</span></td></tr>
</table>
== 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> [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
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== Publication Abstract from PubMed ==
Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (SWELL1) and LRRC8B-E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents across cell types. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here we leverage a fiducial-tagging strategy to determine single-particle cryo-EM structures of heterohexameric LRRC8A:C channels in multiple conformations. Compared to homomers, LRRC8A:C channels show pronounced differences in architecture due to heterotypic LRR interactions that displace subunits away from the conduction axis and poise the channel for activation. Structures and functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. These results provide insight into determinants for heteromeric LRRC8 channel assembly, activity and gating by lipids.

Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.,Kern DM, Bleier J, Mukherjee S, Hill JM, Kossiakoff AA, Isacoff EY, Brohawn SG Nat Struct Mol Biol. 2023 Jun;30(6):841-852. doi: 10.1038/s41594-023-00944-6. , Epub 2023 Mar 16. PMID:36928458<ref>PMID:36928458</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 8dra" style="background-color:#fffaf0;"></div>

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