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6g8z

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Structure of the pore domain of homomeric mLRRC8A volume-regulated anion channel at 3.66 A resolution

6g8z, resolution 3.66Å

Structural highlights

6g8z is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Lrrc8a, Lrrc8 (LK3 transgenic mice)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]^[1] ^[2]

Publication Abstract from PubMed

Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.

Structure of a volume-regulated anion channel of the LRRC8 family.,Deneka D, Sawicka M, Lam AKM, Paulino C, Dutzler R Nature. 2018 May 16. pii: 10.1038/s41586-018-0134-y. doi:, 10.1038/s41586-018-0134-y. PMID:29769723^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J. A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest. 2003 Dec;112(11):1707-13. doi: 10.1172/JCI18937. PMID:14660746 doi:http://dx.doi.org/10.1172/JCI18937
↑ Kumar L, Chou J, Yee CS, Borzutzky A, Vollmann EH, von Andrian UH, Park SY, Hollander G, Manis JP, Poliani PL, Geha RS. Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J Exp Med. 2014 May 5;211(5):929-42. doi: 10.1084/jem.20131379. Epub 2014 Apr 21. PMID:24752297 doi:http://dx.doi.org/10.1084/jem.20131379
↑ Deneka D, Sawicka M, Lam AKM, Paulino C, Dutzler R. Structure of a volume-regulated anion channel of the LRRC8 family. Nature. 2018 May 16. pii: 10.1038/s41586-018-0134-y. doi:, 10.1038/s41586-018-0134-y. PMID:29769723 doi:http://dx.doi.org/10.1038/s41586-018-0134-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6g8z"

@@ Line 3: / Line 3: @@
 <SX load='6g8z' size='340' side='right' viewer='molstar' caption='[[6g8z]], [[Resolution|resolution]] 3.66&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6g8z]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G8Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6g8z]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G8Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6G8Z FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Lrrc8a, Lrrc8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g8z OCA], [http://pdbe.org/6g8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g8z RCSB], [http://www.ebi.ac.uk/pdbsum/6g8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g8z ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6g8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g8z OCA], [http://pdbe.org/6g8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g8z RCSB], [http://www.ebi.ac.uk/pdbsum/6g8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g8z ProSAT]</span></td></tr>
 </table>
 == Function ==

6g8z

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Current revision

Structure of the pore domain of homomeric mLRRC8A volume-regulated anion channel at 3.66 A resolution

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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