Structures and pH-sensing mechanism of the proton-activated chloride channel.

ABSTRACT: The proton-activated chloride channel (PAC) is active across a wide range of mammalian cells and is involved in acid-induced cell death and tissue injury^1-3. PAC has recently been shown to represent a novel and evolutionarily conserved protein family^4,5. Here we present two cryo-electron microscopy structures of human PAC in a high-pH resting closed state and a low-pH proton-bound non-conducting state. PAC is a trimer in which each subunit consists of a transmembrane domain (TMD), which is formed of two helices (TM1 and TM2), and an extracellular domain (ECD). Upon a decrease of pH from 8 to 4, we observed marked conformational changes in the ECD-TMD interface and the TMD. The rearrangement of the ECD-TMD interface is characterized by the movement of the histidine 98

SUBMITTER: Ruan Z 

PROVIDER: S-EPMC7773282 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature