Structure of a volume-regulated anion channel of the LRRC8 familyDeneka, D., Sawicka, M., Lam, A. K. M., Batista Paulino, C. & Dutzler, R., 14-Jun-2018, In : Nature. 558, p. 254-259 6 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||6|
|Publication status||Published - 14-Jun-2018|
- CRYO-ELECTRON MICROSCOPY, X-ray crystallography, LRRC8 family, anion channel