8sxa | pdb_00008sxa

Inward-facing wide conformation of bovine multidrug resistance protein 4 (MRP4) in MSP lipid nanodisc

spinqualitylabelsall models 8sxa, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8sxa is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0AAA9T569_BOVIN Publication Abstract from PubMed 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(1), PGE(2) 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(2+) 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. Structural basis of prostaglandin efflux by MRP4.,Pourmal S, Green E, Bajaj R, Chemmama IE, Knudsen GM, Gupta M, Sali A, Cheng Y, Craik CS, Kroetz DL, Stroud RM Nat Struct Mol Biol. 2024 Apr;31(4):621-632. doi: 10.1038/s41594-023-01176-4. , Epub 2024 Jan 12. PMID:38216659 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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