8SWN

Bovine multidrug resistance protein 4 (MRP4) E1202Q mutant bound to ATP in MSP lipid nanodisc

8SWN の概要

• エントリーDOI: 10.2210/pdb8swn/pdb
• EMDBエントリー: 40821
• 分子名称: ATP binding cassette subfamily C member 4, MAGNESIUM ION, PHOSPHATIDYLETHANOLAMINE, ... (4 entities in total)
• 機能のキーワード: abc transporter, multidrug resistance-associated protein, membrane protein, transport protein
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 151383.32

構造登録者

Pourmal, S.,Stroud, R.M. (登録日: 2023-05-19, 公開日: 2024-01-17, 最終更新日: 2025-05-21)

主引用文献

Pourmal, S.,Green, E.,Bajaj, R.,Chemmama, I.E.,Knudsen, G.M.,Gupta, M.,Sali, A.,Cheng, Y.,Craik, C.S.,Kroetz, D.L.,Stroud, R.M.
Structural basis of prostaglandin efflux by MRP4.
Nat.Struct.Mol.Biol., 31:621-632, 2024

PubMed Abstract: Multidrug resistance protein 4 (MRP4) is a broadly expressed ATP-binding cassette transporter that is unique among the MRP subfamily for transporting prostanoids, a group of signaling molecules derived from unsaturated fatty acids. To better understand the basis of the substrate selectivity of MRP4, we used cryogenic-electron microscopy to determine six structures of nanodisc-reconstituted MRP4 at various stages throughout its transport cycle. Substrate-bound structures of MRP4 in complex with PGE, PGE and the sulfonated-sterol DHEA-S reveal a common binding site that accommodates a diverse set of organic anions and suggest an allosteric mechanism for substrate-induced enhancement of MRP4 ATPase activity. Our structure of a catalytically compromised MRP4 mutant bound to ATP-Mg is outward-occluded, a conformation previously unobserved in the MRP subfamily and consistent with an alternating-access transport mechanism. Our study provides insights into the endogenous function of this versatile efflux transporter and establishes a basis for MRP4-targeted drug design.

PubMed: 38216659
DOI: 10.1038/s41594-023-01176-4

実験手法

ELECTRON MICROSCOPY (3.1 Å)