9LGD

wild-type bovine ABCC1 under an active turnover conformation with unhydrolyzed ATP bound and hydrolyzed ADP released

9LGD の概要

• エントリーDOI: 10.2210/pdb9lgd/pdb
• EMDBエントリー: 63062
• 分子名称: Multidrug resistance-associated protein 1, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: abc transporter, active abcc1, atp, protein transport
• 由来する生物種: Bos taurus (domestic cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 175536.17

構造登録者

Sun, P.P.,Liu, K.X.,Gao, P. (登録日: 2025-01-10, 公開日: 2025-10-01, 最終更新日: 2026-04-15)

主引用文献

Sun, P.,Liu, K.,Zhang, L.,Zhang, Q.,Gao, Y.,Li, Z.,Zhu, Y.,Liu, S.,Zhang, L.,Gao, A.,Gao, P.
Substrate recognition diversity and transport dynamics of ABCC1.
Nat Commun, 16:10499-10499, 2025

PubMed Abstract: ABCC1 is an ATP-binding cassette (ABC) transporter that exports diverse endogenous and exogenous substrates, conferring resistance to many anticancer drugs and mediating various physiological functions. Here, we present ten cryo-EM structures of ABCC1 in different functional states, providing systematic insights into its substrate recognition diversity and transport dynamics. ABCC1 utilizes a plastic bipartite substrate-binding pocket and a substrate-induced conformational flexibility to accommodate molecules with diverse properties, including bimolecular glutathione (GSH)-substrate pairs, GSH conjugates, and GSH-independent cyclic dinucleotides. A herein characterized substrate-releasing intermediate state reveals ATP-mediated overall conformational transitions and detailed pocket reorganization during substrate loading, pre-release, and post-release. Unexpectedly, we identify a sequential nucleotide release mechanism where the hydrolysis product ADP, rather than unhydrolyzed ATP, releases first, priming the transporter for turnover and resetting. Complemented by mutagenesis and functional assays, these findings provide a complete framework for understanding ABCC1's molecular basis and offer a foundation for developing next-generation modulators.

PubMed: 41290683
DOI: 10.1038/s41467-025-65501-9

実験手法

ELECTRON MICROSCOPY (3.29 Å)