| First Author | Deneka D | Year | 2018 |
| Journal | Nature | PubMed ID | 29769723 |
| Mgi Jnum | J:262352 | Mgi Id | MGI:6162376 |
| Doi | 10.1038/s41586-018-0134-y | Citation | Deneka D, et al. (2018) Structure of a volume-regulated anion channel of the LRRC8 family. Nature |
| abstractText | 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. |
