6QEE

Nanodisc reconstituted Human-mouse chimeric ABCB1 (ABCB1HM)-EQ mutant in complex with UIC2 Fab and Zosuquidar.

6QEE の概要

• エントリーDOI: 10.2210/pdb6qee/pdb
• EMDBエントリー: 4536
• 分子名称: ABCB1HM-EQ, UIC2 Antigen Binding Fragment Light chain, UIC2 Antigen Binding Fragment Heavy Chain, ... (7 entities in total)
• 機能のキーワード: abcb1, p-glycoprotein, p-gp, multidrug transporter, abc transporter, zosuquidar, membrane transporter, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 197503.62

構造登録者

Alam, A. (登録日: 2019-01-07, 公開日: 2019-02-27, 最終更新日: 2025-07-09)

主引用文献

Alam, A.,Kowal, J.,Broude, E.,Roninson, I.,Locher, K.P.
Structural insight into substrate and inhibitor discrimination by human P-glycoprotein.
Science, 363:753-756, 2019

PubMed Abstract: ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo-electron microscopy structure of substrate-bound human ABCB1 reconstituted in lipidic nanodiscs, revealing a single molecule of the chemotherapeutic compound paclitaxel (Taxol) bound in a central, occluded pocket. A second structure of inhibited, human-mouse chimeric ABCB1 revealed two molecules of zosuquidar occupying the same drug-binding pocket. Minor structural differences between substrate- and inhibitor-bound ABCB1 sites are amplified toward the nucleotide-binding domains (NBDs), revealing how the plasticity of the drug-binding site controls the dynamics of the adenosine triphosphate-hydrolyzing NBDs. Ordered cholesterol and phospholipid molecules suggest how the membrane modulates the conformational changes associated with drug binding and transport.

PubMed: 30765569
DOI: 10.1126/science.aav7102

実験手法

ELECTRON MICROSCOPY (3.9 Å)