9t35: Difference between revisions

Latest revision as of 08:05, 9 September 2026

Cryo-EM structure of homo-hexameric hLRRC8A L402W

Structural highlights

9t35 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.78Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

LRC8A_HUMAN Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving LRRC8 has been found in a patient with congenital agammaglobulinemia. Translocation t(9;20)(q33.2;q12). The translocation truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of the seventh LRR domains.

Function

LRC8A_HUMAN 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 (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (PubMed:28193731). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). Required for in vivo channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731). Can form functional channels by itself (in vitro) (PubMed:26824658). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746). Also required for T-cell development (By similarity).[UniProtKB:Q80WG5]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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:https://dx.doi.org/10.1172/JCI18937
↑ Qiu Z, Dubin AE, Mathur J, Tu B, Reddy K, Miraglia LJ, Reinhardt J, Orth AP, Patapoutian A. SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell. 2014 Apr 10;157(2):447-458. doi: 10.1016/j.cell.2014.03.024. PMID:24725410 doi:https://dx.doi.org/10.1016/j.cell.2014.03.024
↑ Voss FK, Ullrich F, Munch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science. 2014 May 9;344(6184):634-8. doi: 10.1126/science.1252826. Epub 2014 Apr , 10. PMID:24790029 doi:https://dx.doi.org/10.1126/science.1252826
↑ Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, Kucukosmanoglu A, Xu G, Voss FK, Reincke SM, Stauber T, Blomen VA, Vis DJ, Wessels LF, Brummelkamp TR, Borst P, Rottenberg S, Jentsch TJ. Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J. 2015 Dec 14;34(24):2993-3008. doi: 10.15252/embj.201592409. Epub 2015 Nov, 3. PMID:26530471 doi:https://dx.doi.org/10.15252/embj.201592409
↑ Syeda R, Qiu Z, Dubin AE, Murthy SE, Florendo MN, Mason DE, Mathur J, Cahalan SM, Peters EC, Montal M, Patapoutian A. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell. 2016 Jan 28;164(3):499-511. doi: 10.1016/j.cell.2015.12.031. PMID:26824658 doi:https://dx.doi.org/10.1016/j.cell.2015.12.031
↑ Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ. Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. J Cell Sci. 2017 Mar 15;130(6):1122-1133. doi: 10.1242/jcs.196253. Epub 2017 Feb , 13. PMID:28193731 doi:https://dx.doi.org/10.1242/jcs.196253
↑ 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:https://dx.doi.org/10.1038/s41586-018-0134-y

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1172/JCI18937

[2] Qiu Z, Dubin AE, Mathur J, Tu B, Reddy K, Miraglia LJ, Reinhardt J, Orth AP, Patapoutian A. SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell. 2014 Apr 10;157(2):447-458. doi: 10.1016/j.cell.2014.03.024. PMID:24725410 doi:https://dx.doi.org/10.1016/j.cell.2014.03.024

[3] Voss FK, Ullrich F, Munch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science. 2014 May 9;344(6184):634-8. doi: 10.1126/science.1252826. Epub 2014 Apr , 10. PMID:24790029 doi:https://dx.doi.org/10.1126/science.1252826

[4] Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, Kucukosmanoglu A, Xu G, Voss FK, Reincke SM, Stauber T, Blomen VA, Vis DJ, Wessels LF, Brummelkamp TR, Borst P, Rottenberg S, Jentsch TJ. Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J. 2015 Dec 14;34(24):2993-3008. doi: 10.15252/embj.201592409. Epub 2015 Nov, 3. PMID:26530471 doi:https://dx.doi.org/10.15252/embj.201592409

[5] Syeda R, Qiu Z, Dubin AE, Murthy SE, Florendo MN, Mason DE, Mathur J, Cahalan SM, Peters EC, Montal M, Patapoutian A. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell. 2016 Jan 28;164(3):499-511. doi: 10.1016/j.cell.2015.12.031. PMID:26824658 doi:https://dx.doi.org/10.1016/j.cell.2015.12.031

[6] Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ. Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. J Cell Sci. 2017 Mar 15;130(6):1122-1133. doi: 10.1242/jcs.196253. Epub 2017 Feb , 13. PMID:28193731 doi:https://dx.doi.org/10.1242/jcs.196253

[7] 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:https://dx.doi.org/10.1038/s41586-018-0134-y

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9t35 is ON HOLD  until Paper Publication
+==Cryo-EM structure of homo-hexameric hLRRC8A L402W==
+<StructureSection load='9t35' size='340' side='right'caption='[[9t35]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
-Authors: Bertelli, S., Wang, L., Klussendorf, M., Pusch, M., Dutzler, R., Stauber, T.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9t35]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9T35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9T35 FirstGlance]. <br>
-Description: Cryo-EM structure of homo-hexameric hLRRC8A L402W
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.78&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9t35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9t35 OCA], [https://pdbe.org/9t35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9t35 RCSB], [https://www.ebi.ac.uk/pdbsum/9t35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9t35 ProSAT]</span></td></tr>
-[[Category: Pusch, M]]
+</table>
-[[Category: Wang, L]]
+== Disease ==
-[[Category: Dutzler, R]]
+[https://www.uniprot.org/uniprot/LRC8A_HUMAN LRC8A_HUMAN] Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving LRRC8 has been found in a patient with congenital agammaglobulinemia. Translocation t(9;20)(q33.2;q12). The translocation truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of the seventh LRR domains.
-[[Category: Klussendorf, M]]
+== Function ==
-[[Category: Stauber, T]]
+[https://www.uniprot.org/uniprot/LRC8A_HUMAN LRC8A_HUMAN] 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 (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (PubMed:28193731). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). Required for in vivo channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731). Can form functional channels by itself (in vitro) (PubMed:26824658). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746). Also required for T-cell development (By similarity).[UniProtKB:Q80WG5]<ref>PMID:14660746</ref> <ref>PMID:24725410</ref> <ref>PMID:24790029</ref> <ref>PMID:26530471</ref> <ref>PMID:26824658</ref> <ref>PMID:28193731</ref> <ref>PMID:29769723</ref>
-[[Category: Bertelli, S]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bertelli S]]
+[[Category: Dutzler R]]
+[[Category: Klussendorf M]]
+[[Category: Pusch M]]
+[[Category: Stauber T]]
+[[Category: Wang L]]

9t35: Difference between revisions

Latest revision as of 08:05, 9 September 2026

Cryo-EM structure of homo-hexameric hLRRC8A L402W

Structural highlights

Disease

Function

References

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