| Structural highlights
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.
See Also
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
- ↑ 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:https://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:https://dx.doi.org/10.1038/s41586-018-0134-y
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