Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural and mechanistic basis of substrate transport by the multidrug transporter MRP4.
Journal, issue, pages	Structure, Vol. 31, Issue 11, Page 1407-11418.e6, Year 2023
Publish date	Nov 2, 2023
Authors	Magnus Bloch / Isha Raj / Tillmann Pape / Nicholas M I Taylor /
PubMed Abstract	Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette (ABC) transporter expressed at multiple tissue barriers where it actively extrudes a wide variety of drug compounds. ...Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette (ABC) transporter expressed at multiple tissue barriers where it actively extrudes a wide variety of drug compounds. Overexpression of MRP4 provides resistance to clinically used antineoplastic agents, making it a highly attractive therapeutic target for countering multidrug resistance. Here, we report cryo-EM structures of multiple physiologically relevant states of lipid bilayer-embedded human MRP4, including complexes between MRP4 and two widely used chemotherapeutic agents and a complex between MRP4 and its native substrate. The structures display clear similarities and distinct differences in the coordination of these chemically diverse substrates and, in combination with functional and mutational analysis, reveal molecular details of the transport mechanism. Our study provides key insights into the unusually broad substrate specificity of MRP4 and constitutes an important contribution toward a general understanding of multidrug transporters.
External links	Structure / PubMed:37683641
Methods	EM (single particle)
Resolution	3.0 - 5.5 Å
Structure data	16088 8bjf EMDB-16088, PDB-8bjf: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) Method: EM (single particle) / Resolution: 3.0 Å 16292 8bwo EMDB-16292: Cryo-EM structure of nanodisc-reconstituted human MRP4 withE1202Q mutation (outward-facing occluded conformation) PDB-8bwo: Cryo-EM structure of nanodisc-reconstituted human MRP4 with E1202Q mutation (outward-facing occluded conformation) Method: EM (single particle) / Resolution: 3.2 Å 16293 8bwp EMDB-16293, PDB-8bwp: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with methotrexate) Method: EM (single particle) / Resolution: 3.6 Å 16294 8bwq EMDB-16294, PDB-8bwq: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with topotecan) Method: EM (single particle) / Resolution: 3.9 Å 16295 8bwr EMDB-16295, PDB-8bwr: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with prostaglandin E2) Method: EM (single particle) / Resolution: 4.0 Å EMDB-16296: Cryo-EM structure of native nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) - no nucleotides/substrates added Method: EM (single particle) / Resolution: 3.3 Å EMDB-16297: Cryo-EM structure of minimal nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) - no nucleotides/substrates added Method: EM (single particle) / Resolution: 5.5 Å
Chemicals	ChemComp-CLR: CHOLESTEROL ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-MTX: METHOTREXATE / chemotherapyYM ChemComp-TTC: (S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE / medication, inhibitorYM ChemComp-P2E: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / medicationYM
Source	homo sapiens (human)
Keywords	TRANSLOCASE / ABC transporter / ABCC4 / MRP4 / Topotecan bound / PGE2 bound ABC transporter