The structural basis of the pH-homeostasis mediated by the Cl^-/HCO₃^- exchanger, AE2.

ABSTRACT: The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH to catalyze the exchange between the intracellular HCO₃^- and extracellular Cl^-, thereby maintaining the pH-homeostasis. Here, we determine the cryo-EM structures of human AE2 in five major operating states and one transitional hybrid state. Among those states, the AE2 shows the inward-facing, outward-facing, and intermediate conformations, as well as the substrate-binding pockets at two sides of the cell membrane. Furthermore, critical structural features were identified showing an interlock mechanism for interactions among the cytoplasmic N-terminal domain and

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC10066210 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature