8JNJ

Structure of R932A/K1147A/H1148A mutant AE2

8JNJ の概要

• エントリーDOI: 10.2210/pdb8jnj/pdb
• EMDBエントリー: 36449
• 分子名称: Anion exchange protein 2 (1 entity in total)
• 機能のキーワード: ae2, slc4a2, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 273931.28

構造登録者

Yin, Y.X.,Ding, D. (登録日: 2023-06-06, 公開日: 2024-02-07)

主引用文献

Zhang, W.,Ding, D.,Lu, Y.,Chen, H.,Jiang, P.,Zuo, P.,Wang, G.,Luo, J.,Yin, Y.,Luo, J.,Yin, Y.
Structural and functional insights into the lipid regulation of human anion exchanger 2.
Nat Commun, 15:759-759, 2024

PubMed Abstract: Anion exchanger 2 (AE2) is an electroneutral Na-independent Cl/HCO 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 PIP and a 3.3 Å full-length mutant AE2 structure in the resting state without PIP. We demonstrate that PIP at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PIP binding site leads to the displacement of TM7 and further stabilizes the interaction between the TMD and the NTD. Reduced substrate transport activity and conformation similar to AE2 in acidic pH indicating the central contribution of PIP to the function of AE2.

PubMed: 38272905
DOI: 10.1038/s41467-024-44966-0

実験手法

ELECTRON MICROSCOPY (3.3 Å)