Jane Coffin Childs Memorial Fund for Medical Research
米国
引用
ジャーナル: Cell / 年: 2018 タイトル: ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1. 著者: Zachary Lee Johnson / Jue Chen / 要旨: 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 ...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.
RESIDUES 30-194, CORRESPONDING TO TMD0, ARE MODELED AS POLY- ALANINE (POLY UNK). THE REGISTER IN ...RESIDUES 30-194, CORRESPONDING TO TMD0, ARE MODELED AS POLY- ALANINE (POLY UNK). THE REGISTER IN THIS REGION COULD NOT BE CONFIDENTLY ESTABLISHED AND THUS THE NUMBERING ASSIGNED TO THE RESIDUES IS PUTATIVE. THE POLY-ALANINE REGIONS HAVE BEEN RENAMED AS UNKNOW
解像度: 3.14 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 354752 / 対称性のタイプ: POINT
原子モデル構築
プロトコル: FLEXIBLE FIT / 空間: RECIPROCAL
精密化
解像度: 3.14→142 Å / Cor.coef. Fo:Fc: 0.969 / ESU R: 0.43 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Rfactor
反射数
%反射
Rwork
0.29701
-
-
obs
0.29701
89483
99.99 %
溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK