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Publication Abstract from PubMed

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 HCO(3)(-) 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 the transmembrane domain and the self-inhibitory effect of the C-terminal loop. The structural and cell-based functional assay collectively demonstrate the dynamic process of the anion exchange across membranes and provide the structural basis for the pH-sensitive pH-rebalancing activity of AE2.

The structural basis of the pH-homeostasis mediated by the Cl(-)/HCO(3)(-) exchanger, AE2.,Zhang Q, Jian L, Yao D, Rao B, Xia Y, Hu K, Li S, Shen Y, Cao M, Qin A, Zhao J, Cao Y Nat Commun. 2023 Mar 31;14(1):1812. doi: 10.1038/s41467-023-37557-y. PMID:37002221^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.