EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis of prostaglandin efflux by MRP4.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 31, Issue 4, Page 621-632, Year 2024
掲載日	2024年1月12日
著者	Sergei Pourmal / Evan Green / Ruchika Bajaj / Ilan E Chemmama / Giselle M Knudsen / Meghna Gupta / Andrej Sali / Yifan Cheng / Charles S Craik / Deanna L Kroetz / Robert M Stroud /
PubMed 要旨	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 ...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.
リンク	Nat Struct Mol Biol / PubMed:38216659 / PubMed Central
手法	EM (単粒子)
解像度	2.7 - 3.5 Å
構造データ	40821 8swn EMDB-40821, PDB-8swn: Bovine multidrug resistance protein 4 (MRP4) E1202Q mutant bound to ATP in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 3.1 Å 40826 8sx7 EMDB-40826, PDB-8sx7: Bovine multidrug resistance protein 4 (MRP4) bound to DHEA-S in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 2.7 Å 40827 8sx8 EMDB-40827, PDB-8sx8: Bovine multidrug resistance protein 4 (MRP4) bound to prostaglandin E1 in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 3.5 Å 40828 8sx9 EMDB-40828, PDB-8sx9: Inward-facing narrow conformation of bovine multidrug resistance protein 4 (MRP4) in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 3.3 Å 40829 8sxa EMDB-40829, PDB-8sxa: Inward-facing wide conformation of bovine multidrug resistance protein 4 (MRP4) in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 3.3 Å 40830 8sxb EMDB-40830, PDB-8sxb: Bovine multidrug resistance protein 4 (MRP4) bound to prostaglandin E2 in MSP lipid nanodisc 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-PTY: PHOSPHATIDYLETHANOLAMINE / リン脂質YM ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-ZWY: 17-oxoandrost-5-en-3beta-yl hydrogen sulfate / デヒドロエピアンドロステロンスルファ-ト ChemComp-HOH: WATER ChemComp-XPG: 7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid / プロスタグランジンE₁ / 薬剤YM ChemComp-P2E: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / プロスタグランジンE₂ / 薬剤YM
由来	bos taurus (ウシ) bos indicus (哺乳類)
キーワード	TRANSPORT PROTEIN / ABC transporter / multidrug resistance-associated protein / membrane protein