6BHU

Cryo-EM structure of ATP-bound, outward-facing bovine multidrug resistance protein 1 (MRP1)

6BHU の概要

• エントリーDOI: 10.2210/pdb6bhu/pdb
• 関連するPDBエントリー: 5UJ9 5UJA
• EMDBエントリー: 7099
• 分子名称: Multidrug resistance-associated protein 1, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: abc transporter, multidrug resistance, outward facing, transport protein
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 185297.00

構造登録者

Johnson, Z.L.,Chen, J. (登録日: 2017-10-31, 公開日: 2017-12-27, 最終更新日: 2024-03-13)

主引用文献

Johnson, Z.L.,Chen, J.
ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1.
Cell, 172:81-89.e10, 2018

PubMed Abstract: The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to chemotherapy. Previously, we have shown that intracellular substrates are recruited to a bipartite binding site when the transporter rests in an inward-facing conformation. A key question remains: how are high-affinity substrates transferred across the membrane and released outside the cell? Using electron cryomicroscopy, we show here that ATP binding opens the transport pathway to the extracellular space and reconfigures the substrate-binding site such that it relinquishes its affinity for substrate. Thus, substrate is released prior to ATP hydrolysis. With this result, we now have a complete description of the conformational cycle that enables substrate transfer in a eukaryotic ABC exporter.

PubMed: 29290467
DOI: 10.1016/j.cell.2017.12.005

実験手法

ELECTRON MICROSCOPY (3.14 Å)