Structural and functional insights into the lipid regulation of human anion exchanger 2.

ABSTRACT: Anion exchanger 2 (AE2) is an electroneutral Na⁺-independent Cl^-/HCO₃^- exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, including transepithelial acid-base secretion and osteoclastogenesis. Both the transmembrane domains (TMDs) and the N-terminal cytoplasmic domain (NTD) are involved in regulation of AE2 activity. However, the regulatory mechanism remains unclear. Here, we report a 3.2 Å cryo-EM structure of the AE2 TMDs in complex with PIP₂ and a 3.3 Å full-length mutant AE2 structure in the resting state without PIP₂. We demonstrate that PIP₂ at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PI

SUBMITTER: Zhang W 

PROVIDER: S-EPMC10810954 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature