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Open data
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Basic information
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Title | ATP-bound hMRP5 outward-open | |||||||||
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![]() | ATP-bound hMRP5 outward-open / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transport ...purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transport / glutathione transmembrane transporter activity / heme 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 / Paracetamol ADME / xenobiotic transport / 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 | single particle reconstruction / cryo EM / Resolution: 3.94 Å | |||||||||
![]() | Liu ZM / 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 97.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.1 KB 15.1 KB | Display Display | ![]() |
Images | ![]() | 45.5 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 95.5 MB 95.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8kciMC ![]() 8wi0C ![]() 8wi2C ![]() 8wi3C ![]() 8wi4C ![]() 8wi5C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37105_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37105_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : ATP-bound hMRP5 outward-open
Entire | Name: ATP-bound hMRP5 outward-open |
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Components |
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-Supramolecule #1: ATP-bound hMRP5 outward-open
Supramolecule | Name: ATP-bound hMRP5 outward-open / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: ATP-binding cassette sub-family C member 5
Macromolecule | Name: ATP-binding cassette sub-family C member 5 / type: protein_or_peptide / ID: 1 / Details: ATP-bound hMRP5 / Number of copies: 1 / Enantiomer: LEVO EC number: Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 160.815812 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS LDASMHSQLR ILDEEHPKGK YHHGLSALK PIRTTSKHQH PVDNAGLFSC MTFSWLSSLA RVAHKKGELS MEDVWSLSKH ESSDVNCRRL ERLWQEELNE V GPDAASLR ...String: MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS LDASMHSQLR ILDEEHPKGK YHHGLSALK PIRTTSKHQH PVDNAGLFSC MTFSWLSSLA RVAHKKGELS MEDVWSLSKH ESSDVNCRRL ERLWQEELNE V GPDAASLR RVVWIFCRTR LILSIVCLMI TQLAGFSGPA FMVKHLLEYT QATESNLQYS LLLVLGLLLT EIVRSWSLAL TW ALNYRTG VRLRGAILTM AFKKILKLKN IKEKSLGELI NICSNDGQRM FEAAAVGSLL AGGPVVAILG MIYNVIILGP TGF LGSAVF ILFYPAMMFA SRLTAYFRRK CVAATDERVQ KMNEVLTYIK FIKMYAWVKA FSQSVQKIRE EERRILEKAG YFQS ITVGV APIVVVIASV VTFSVHMTLG FDLTAAQAFT VVTVFNSMTF ALKVTPFSVK SLSEASVAVD RFKSLFLMEE VHMIK NKPA SPHIKIEMKN ATLAWDSSHS SIQNSPKLTP KMKKDKRASR GKKEKVRQLQ RTEHQAVLAE QKGHLLLDSD ERPSPE EEE GKHIHLGHLR LQRTLHSIDL EIQEGKLVGI CGSVGSGKTS LISAILGQMT LLEGSIAISG TFAYVAQQAW ILNATLR DN ILFGKEYDEE RYNSVLNSCC LRPDLAILPS SDLTEIGERG ANLSGGQRQR ISLARALYSD RSIYILDDPL SALCAHVG N HIFNSAIRKH LKSKTVLFVT HQLQYLVDCD EVIFMKEGCI TERGTHEELM NLNGDYATIF NNLLLGETPP VEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSG NTTVTRGNET SVSDSMKDNP HMQYYASIYA LSMAVMLILK AIRGVVFVKG TLRASSRLHD ELFRRILRSP M KFFDTTPT GRILNRFSKD MDEVDVRLPF QAEMFIQNVI LVFFCVGMIA GVFPWFLVAV GPLVILFSVL HIVSRVLIRE LK RLDNITQ SPFLSHITSS IQGLATIHAY NKGQEFLHRY QELLDDNQAP FFLFTCAMRW LAVRLDLISI ALITTTGLMI VLM HGQIPP AYAGLAISYA VQLTGLFQFT VRLASETEAR FTSVERINHY IKTLSLEAPA RIKNKAPSPD WPQEGEVTFE NAEM RYREN LPLVLKKVSF TIKPKEKIGI VGRTGSGKSS LGMALFRLVE LSGGCIKIDG VRISDIGLAD LRSKLSIIPQ EPVLF SGTV RSNLDPFNQY TEDQIWDALE RTHMKECIAQ LPLKLESEVM ENGDNFSVGE RQLLCIARAL LRHCKILILD QATAAM DTE TDLLIQETIR EAFADCTMLT IACRLHTVLG SDRIMVLAQG QVVEFDTPSV LLSNDSSRFY AMFAAAENKV AVKG UniProtKB: ATP-binding cassette sub-family C member 5 |
-Macromolecule #2: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 2 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.94 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1397085 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |