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Yorodumi- EMDB-8559: Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8559 | ||||||||||||
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Title | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||
Map data | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||
Sample |
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Keywords | ABC transporter / multidrug resistance / TRANSPORT PROTEIN | ||||||||||||
Function / homology | Function and homology information Sphingolipid de novo biosynthesis / Heme degradation / Synthesis of Leukotrienes (LT) and Eoxins (EX) / cyclic nucleotide transport / Transport of RCbl within the body / Paracetamol ADME / leukotriene transport / glutathione transmembrane transport / glutathione transmembrane transporter activity / ABC-type glutathione-S-conjugate transporter ...Sphingolipid de novo biosynthesis / Heme degradation / Synthesis of Leukotrienes (LT) and Eoxins (EX) / cyclic nucleotide transport / Transport of RCbl within the body / Paracetamol ADME / leukotriene transport / glutathione transmembrane transport / glutathione transmembrane transporter activity / ABC-type glutathione-S-conjugate transporter / ABC-type glutathione S-conjugate transporter activity / ABC-family proteins mediated transport / Cytoprotection by HMOX1 / ABC-type xenobiotic transporter / xenobiotic transport / ABC-type xenobiotic transporter activity / lipid transport / xenobiotic transmembrane transporter activity / ABC-type transporter activity / positive regulation of inflammatory response / basolateral plasma membrane / response to xenobiotic stimulus / ATP hydrolysis activity / ATP binding Similarity search - Function | ||||||||||||
Biological species | Bos taurus (cattle) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.49 Å | ||||||||||||
Authors | Johnson ZL / Chen J | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Cell / Year: 2017 Title: Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1. Authors: Zachary Lee Johnson / Jue Chen / Abstract: The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several ...The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 Å without any added substrate and a complex form at 3.3 Å with one of its physiological substrates, leukotriene C. These structures show that by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with different chemical structures. We also observed large conformational changes induced by leukotriene C, explaining how substrate binding primes the transporter for ATP hydrolysis. Structural comparison of MRP1 and P-glycoprotein advances our understanding of the common and unique properties of these two important molecules in multidrug resistance to chemotherapy. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8559.map.gz | 199.6 MB | EMDB map data format | |
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Header (meta data) | emd-8559-v30.xml emd-8559.xml | 22.1 KB 22.1 KB | Display Display | EMDB header |
Images | emd_8559.png | 152.5 KB | ||
Filedesc metadata | emd-8559.cif.gz | 6.7 KB | ||
Others | emd_8559_additional.map.gz emd_8559_half_map_1.map.gz emd_8559_half_map_2.map.gz | 194.1 MB 199.6 MB 199.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8559 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8559 | HTTPS FTP |
-Validation report
Summary document | emd_8559_validation.pdf.gz | 892.6 KB | Display | EMDB validaton report |
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Full document | emd_8559_full_validation.pdf.gz | 892.2 KB | Display | |
Data in XML | emd_8559_validation.xml.gz | 16 KB | Display | |
Data in CIF | emd_8559_validation.cif.gz | 18.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8559 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8559 | HTTPS FTP |
-Related structure data
Related structure data | 5uj9MC 8560C 5ujaC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-10802 (Title: Cryo-electron microscopy reconstruction of apo bovine MRP1 Data size: 804.5 Data #1: Unaligned and uncorrected multiframe movies of bovine apo MRP1 [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_8559.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.38542 Å / Y: 0.28646 Å / Z: 0.28646 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1)
File | emd_8559_additional.map | ||||||||||||
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Annotation | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1)
File | emd_8559_half_map_1.map | ||||||||||||
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Annotation | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1)
File | emd_8559_half_map_2.map | ||||||||||||
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Annotation | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : bovine multidrug resistance protein 1 (MRP1)
Entire | Name: bovine multidrug resistance protein 1 (MRP1) |
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Components |
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-Supramolecule #1: bovine multidrug resistance protein 1 (MRP1)
Supramolecule | Name: bovine multidrug resistance protein 1 (MRP1) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 170 KDa |
-Macromolecule #1: bovine multidrug resistance protein 1 (MRP1),Multidrug resistance...
Macromolecule | Name: bovine multidrug resistance protein 1 (MRP1),Multidrug resistance-associated protein 1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 159.701922 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) ...String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)PNPCPESS ASFLSRI TF WWITGMMVQG YRQPLESTDL WSLNKEDTSE QVVPVLVKNW KKECAKSRKQ PVKIVYSSKD PAKPKGSSKV DVNEEAEA L IVKCPQKERD PSLFKVLYKT FGPYFLMSFL FKAVHDLMMF AGPEILKLLI NFVNDKKAPE WQGYFYTALL FISACLQTL VLHQYFHICF VSGMRIKTAV IGAVYRKALV ITNAARKSST VGEIVNLMSV DAQRFMDLAT YINMIWSAPL QVILALYLLW LNLGPSVLA GVAVMVLMVP LNAVMAMKTK TYQVAHMKSK DNRIKLMNEI LNGIKVLKLY AWELAFKDKV LAIRQEELKV L KKSAYLAA VGTFTWVCTP FLVALSTFAV YVTVDENNIL DAQKAFVSLA LFNILRFPLN ILPMVISSIV QASVSLKRLR VF LSHEDLD PDSIQRRPIK DAGATNSITV KNATFTWARN DPPTLHGITF SVPEGSLVAV VGQVGCGKSS LLSALLAEMD KVE GHVTVK GSVAYVPQQA WIQNISLREN ILFGRQLQER YYKAVVEACA LLPDLEILPS GDRTEIGEKG VNLSGGQKQR VSLA RAVYC DSDVYLLDDP LSAVDAHVGK HIFENVIGPK GLLKNKTRLL VTHAISYLPQ MDVIIVMSGG KISEMGSYQE LLARD GAFA EFLRTYASAE QEQGQPEDGL AGVGGPGKEV KQMENGMLVT DTAGKQMQRQ LSSSSSYSRD VSQHHTSTAE LRKPGP TEE TWKLVEADKA QTGQVKLSVY WDYMKAIGLF ISFLSIFLFL CNHVASLVSN YWLSLWTDDP IVNGTQEHTQ VRLSVYG AL GISQGITVFG YSMAVSIGGI FASRRLHLDL LHNVLRSPIS FFERTPSGNL VNRFSKELDT VDSMIPQVIK MFMGSLFN V IGACIIILLA TPMAAVIIPP LGLIYFFVQR FYVASSRQLK RLESVSRSPV YSHFNETLLG VSVIRAFEEQ ERFIRQSDL KVDENQKAYY PSIVANRWLA VRLECVGNCI VLFASLFAVI SRHSLSAGLV GLSVSYSLQV TTYLNWLVRM SSEMETNIVA VERLKEYSE TEKEAPWQIQ DMAPPKDWPQ VGRVEFRDYG LRYREDLDLV LKHINVTIDG GEKVGIVGRT GAGKSSLTLG L FRIKESAE GEIIIDDINI AKIGLHDLRF KITIIPQDPV LFSGSLRMNL DPFSQYSDEE VWTSLELAHL KGFVSALPDK LN HECAEGG ENLSVGQRQL VCLARALLRK TKILVLDEAT AAVDLETDDL IQSTIRTQFD DCTVLTIAHR LNTIMDYTRV IVL DKGEIQ EWGSPSDLLQ QRGLFYSMAK DSGLVSNSLE VLFQ UniProtKB: Multidrug resistance-associated protein 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.4 mg/mL | ||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 400-mesh Au Holey Carbon Grids / Material: GOLD / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 12 sec. / Pretreatment - Atmosphere: AIR | ||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 80.0 K / Max: 100.0 K |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3710 pixel / Digitization - Dimensions - Height: 3838 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 2232 / Average exposure time: 7.0 sec. / Average electron dose: 84.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 37000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL |
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Output model | PDB-5uj9: |