7TY4

Cryo-EM structure of human Anion Exchanger 1

7TY4 の概要

• エントリーDOI: 10.2210/pdb7ty4/pdb
• EMDBエントリー: 26165
• 分子名称: Band 3 anion transport protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL, ... (6 entities in total)
• 機能のキーワード: transmembrane, transport 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: 209890.47

構造登録者

Capper, M.J.,Mathiharan, Y.K.,Yang, S.,Stone, A.C.,Wacker, D. (登録日: 2022-02-11, 公開日: 2023-08-16, 最終更新日: 2024-10-16)

主引用文献

Capper, M.J.,Yang, S.,Stone, A.C.,Vatansever, S.,Zilberg, G.,Mathiharan, Y.K.,Habib, R.,Hutchinson, K.,Zhao, Y.,Schlessinger, A.,Mezei, M.,Osman, R.,Zhang, B.,Wacker, D.
Substrate binding and inhibition of the anion exchanger 1 transporter.
Nat.Struct.Mol.Biol., 30:1495-1504, 2023

PubMed Abstract: Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition.

PubMed: 37679563
DOI: 10.1038/s41594-023-01085-6

実験手法

ELECTRON MICROSCOPY (2.99 Å)