9OE2

Zebrafish Abcb4 in IF-medium conformation in the presence of Tariquidar (TQR-IF-Medium)

9OE2 の概要

• エントリーDOI: 10.2210/pdb9oe2/pdb
• EMDBエントリー: 70384
• 分子名称: ATP-binding cassette, sub-family B (MDR/TAP), member 4, MAGNESIUM ION, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• 機能のキーワード: multidrug resistance, zebrafish abcb4, p-gp, tariquidar, transport protein
• 由来する生物種: Danio rerio (zebrafish)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 144434.92

構造登録者

Zhan, J.,Xia, D. (登録日: 2025-04-28, 公開日: 2026-06-03, 最終更新日: 2026-08-05)

主引用文献

Zhan, J.,Hsieh, C.M.,Esser, L.,Lang, Z.C.,Morton, A.J.,Robey, R.,Zhou, F.,Ambudkar, S.V.,Huang, R.K.,Gottesman, M.M.,Xia, D.
Functional implications of the conformational landscape of a multidrug transporter revealed by Zebrafish Abcb4 structures.
Nat Commun, 17:-, 2026

PubMed Abstract: The hallmark of multidrug resistance conferred by the human ABC transporter ABCB1 (hP-gp) is the recognition and efflux of a diverse range of drugs, though the precise mechanism of polyspecificity remains unresolved. In aquatic animals such as zebrafish, Abcb4, a functional homolog of hP-gp, plays a vital role in surviving environmental toxicants. Here, we show that DrAbcb4 exhibits comparable basal and drug-stimulated ATPase activity to hP-gp. Using cryo-EM, we capture five inward-facing DrAbcb4 conformations with varying separations between its two lobes, illustrating its open-and-close motion. The range of separation exceeds that seen in published P-gp structures that appear to be conformationally restricted. This global open-and-close motion is coupled with individual helix movement, resulting in a highly fluid substrate-binding pocket. These dynamic changes, likely underlying the polyspecificity of substrate recognition, predict unconventional protein-ligand interactions that are supported by structures of DrAbcb4 bound to the P-gp inhibitors tariquidar and elacridar, and the substrate vincristine.

PubMed: 42218127
DOI: 10.1038/s41467-026-73751-4

実験手法

ELECTRON MICROSCOPY (3.18 Å)