8GVF

The outward-facing structure of hAE2 in basic pH

Summary for 8GVF

• Entry DOI: 10.2210/pdb8gvf/pdb
• EMDB information: 34292
• Descriptor: Anion exchange protein 2 (1 entity in total)
• Functional Keywords: chloride and bicarbonate transporter human-ae2, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 274353.81

Authors

Zhang, Q.,Jian, L.,Yao, D.,Rao, B.,Hu, K.,Xia, Y.,Cao, Y. (deposition date: 2022-09-15, release date: 2023-04-12, Last modification date: 2024-06-19)

Primary citation

Zhang, Q.,Jian, L.,Yao, D.,Rao, B.,Xia, Y.,Hu, K.,Li, S.,Shen, Y.,Cao, M.,Qin, A.,Zhao, J.,Cao, Y.
The structural basis of the pH-homeostasis mediated by the Cl - /HCO 3 - exchanger, AE2.
Nat Commun, 14:1812-1812, 2023

PubMed 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 HCO 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.

PubMed: 37002221
DOI: 10.1038/s41467-023-37557-y

Experimental method

ELECTRON MICROSCOPY (3.09 Å)