6VXJ

Structure of ABCG2 bound to SN38

6VXJ の概要

• エントリーDOI: 10.2210/pdb6vxj/pdb
• EMDBエントリー: 21436 21437 21438 21439 21440 21441
• 分子名称: Broad substrate specificity ATP-binding cassette transporter ABCG2, CHOLESTEROL, 7-ethyl-10-hydroxycamptothecin (3 entities in total)
• 機能のキーワード: abcg2, sn38, abc transporter, nanodisc, translocase
• 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: 145937.42

構造登録者

Orlando, B.J.,Liao, M. (登録日: 2020-02-22, 公開日: 2020-05-13, 最終更新日: 2025-06-04)

主引用文献

Orlando, B.J.,Liao, M.
ABCG2 transports anticancer drugs via a closed-to-open switch.
Nat Commun, 11:2264-2264, 2020

PubMed Abstract: ABCG2 is an ABC transporter that extrudes a variety of compounds from cells, and presents an obstacle in treating chemotherapy-resistant cancers. Despite recent structural insights, no anticancer drug bound to ABCG2 has been resolved, and the mechanisms of multidrug transport remain obscure. Such a gap of knowledge limits the development of novel compounds that block or evade this critical molecular pump. Here we present single-particle cryo-EM studies of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics. Without the binding of conformation-selective antibody fragments or inhibitors, the resting ABCG2 adopts a closed conformation. Our cryo-EM, biochemical, and functional analyses reveal the binding mode of three chemotherapeutic compounds, demonstrate how these molecules open the closed conformation of the transporter, and establish that imatinib is particularly effective in stabilizing the inward facing conformation of ABCG2. Together these studies reveal the previously unrecognized conformational cycle of ABCG2.

PubMed: 32385283
DOI: 10.1038/s41467-020-16155-2

実験手法

ELECTRON MICROSCOPY (4.1 Å)