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Open data
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Basic information
Entry | Database: PDB / ID: 8wi5 | ||||||
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Title | M5PI-bound hMRP5 | ||||||
![]() | (ATP-binding cassette sub-family C member 5) x 2 | ||||||
![]() | MEMBRANE PROTEIN / M5PI-bound hMRP5 | ||||||
Function / homology | ![]() purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / heme transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity ...purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / heme transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transporter activity / glutathione transmembrane transport / hyaluronan biosynthetic process / ATPase-coupled inorganic anion transmembrane transporter activity / organic anion transmembrane transporter activity / xenobiotic transmembrane transport / export across plasma membrane / ABC-type xenobiotic transporter / xenobiotic transport / Paracetamol ADME / ABC-type xenobiotic transporter activity / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / Azathioprine ADME / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / ATPase-coupled transmembrane transporter activity / xenobiotic metabolic process / ABC-family proteins mediated transport / transmembrane transport / Golgi lumen / basolateral plasma membrane / endosome membrane / apical plasma membrane / ATP hydrolysis activity / ATP binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.46 Å | ||||||
![]() | Liu, Z.M. / Huang, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Inhibition and transport mechanisms of the ABC transporter hMRP5. Authors: Ying Huang / Chenyang Xue / Ruiqian Bu / Cang Wu / Jiachen Li / Jinqiu Zhang / Jinyu Chen / Zhaoying Shi / Yonglong Chen / Yong Wang / Zhongmin Liu / ![]() Abstract: Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, ...Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 248 KB | Display | ![]() |
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PDB format | ![]() | 191.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 42.8 KB | Display | |
Data in CIF | ![]() | 63.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 37558MC ![]() 8kciC ![]() 8wi0C ![]() 8wi2C ![]() 8wi3C ![]() 8wi4C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 150243.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O15440, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter |
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#2: Protein/peptide | Mass: 2519.765 Da / Num. of mol.: 1 Fragment: CYS-GLN-ASP-ALA-LEU-GLU-THR-ALA-ALA-ARG-ALA-GLU-GLY-LEU-SER-LEU-ASP-ALA-SER-MET-HIS-SER-GLN-LEU Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O15440, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: M5PI-bound hMRP5 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 944572 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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