Structure of a volume-regulated anion channel of the LRRC8 family

Article

关键词: GAP-JUNCTION CHANNEL;    ESSENTIAL COMPONENT;    INDUCED RELEASE;    AMINO-ACIDS;    PROTEIN;    MODEL;    CURRENTS;    PHOSPHORYLATION;    PERMEABILITY;    ACTIVATION;   

DOI  :  10.1038/s41586-018-0134-y

来源: SCIE

【 摘 要 】

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 leucinerich 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.

【 授权许可】

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