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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Cryo-EM structure of human ABCC4 | |||||||||
![]() | app-ABCC4 | |||||||||
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![]() | ABC transporter MRP / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() guanine nucleotide transmembrane transporter activity / 15-hydroxyprostaglandin dehydrogenase (NAD+) activity / purine nucleotide transmembrane transporter activity / cAMP transport / urate transport / ABC-type bile acid transporter activity / platelet dense granule membrane / leukotriene transport / prostaglandin transport / glutathione transmembrane transporter activity ...guanine nucleotide transmembrane transporter activity / 15-hydroxyprostaglandin dehydrogenase (NAD+) activity / purine nucleotide transmembrane transporter activity / cAMP transport / urate transport / ABC-type bile acid transporter activity / platelet dense granule membrane / leukotriene transport / prostaglandin transport / glutathione transmembrane transporter activity / prostaglandin transmembrane transporter activity / ABC-type glutathione-S-conjugate transporter / urate transmembrane transporter activity / ABC-type glutathione S-conjugate transporter activity / platelet degranulation / ATPase-coupled inorganic anion transmembrane transporter activity / external side of apical plasma membrane / xenobiotic transmembrane transport / export across plasma membrane / ABC-type xenobiotic transporter / prostaglandin secretion / Paracetamol ADME / bile acid and bile salt 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 / cilium assembly / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / xenobiotic metabolic process / ABC-family proteins mediated transport / transmembrane transport / Platelet degranulation / basolateral plasma membrane / apical plasma membrane / nucleolus / Golgi apparatus / ATP hydrolysis activity / ATP binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.84 Å | |||||||||
![]() | Zhang PF / Liu Z | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The ATP-bound inward-open conformation of ABCC4 reveals asymmetric ATP binding for substrate transport. Authors: Yue Zhu / Xiaoke Xing / Fuxing Wang / Luojun Chen / Chunhui Zhong / Xiting Lu / Zhanwang Yu / Yongbo Yang / Yi Yao / Qibin Song / Suxia Han / Zheng Liu / Pingfeng Zhang / ![]() Abstract: The multidrug resistance-associated protein (MRP) ABCC4 facilitates substrate transport across the cytoplasmic membrane, crucial for normal physiology and mediating multidrug resistance in tumor ...The multidrug resistance-associated protein (MRP) ABCC4 facilitates substrate transport across the cytoplasmic membrane, crucial for normal physiology and mediating multidrug resistance in tumor cells. Despite intensive studies on MRPs, ABCC4's transport mechanism remains incompletely understood. In this study, we unveiled an inward-open conformation with an ATP bound to degenerate NBD1. Additionally, we captured the structure with both ATP and substrate co-bound in the inward-open state. Our findings uncover the asymmetric ATP binding in ABCC4 and provide insights into substrate binding and transport mechanisms. ATP binding to NBD1 is parallel to substrate binding to ABCC4, and is a prerequisite for ATP-bound NBD2-induced global conformational changes. Our findings shed new light on targeting ABCC4 in combination with anticancer therapy. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.3 KB 17.3 KB | Display Display | ![]() |
Images | ![]() | 71.6 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8xokMC ![]() 8xolC ![]() 8xomC 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
File | ![]() | ||||||||||||||||||||
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Annotation | app-ABCC4 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: app-ABCC4 halfA
File | emd_38532_half_map_1.map | ||||||||||||
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Annotation | app-ABCC4 halfA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: app-ABCC4 halfB
File | emd_38532_half_map_2.map | ||||||||||||
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Annotation | app-ABCC4 halfB | ||||||||||||
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Density Histograms |
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Sample components
-Entire : apo human ABCC4
Entire | Name: apo human ABCC4 |
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Components |
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-Supramolecule #1: apo human ABCC4
Supramolecule | Name: apo human ABCC4 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 149.5 KDa |
-Macromolecule #1: ATP-binding cassette sub-family C member 4
Macromolecule | Name: ATP-binding cassette sub-family C member 4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ABC-type xenobiotic transporter |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 149.693922 KDa |
Recombinant expression | Organism: Mammalian expression vector Flag-MCS-pcDNA3.1 (others) |
Sequence | String: MLPVYQEVKP NPLQDANLCS RVFFWWLNPL FKIGHKRRLE EDDMYSVLPE DRSQHLGEEL QGFWDKEVLR AENDAQKPSL TRAIIKCYW KSYLVLGIFT LIEESAKVIQ PIFLGKIINY FENYDPMDSV ALNTAYAYAT VLTFCTLILA ILHHLYFYHV Q CAGMRLRV ...String: MLPVYQEVKP NPLQDANLCS RVFFWWLNPL FKIGHKRRLE EDDMYSVLPE DRSQHLGEEL QGFWDKEVLR AENDAQKPSL TRAIIKCYW KSYLVLGIFT LIEESAKVIQ PIFLGKIINY FENYDPMDSV ALNTAYAYAT VLTFCTLILA ILHHLYFYHV Q CAGMRLRV AMCHMIYRKA LRLSNMAMGK TTTGQIVNLL SNDVNKFDQV TVFLHFLWAG PLQAIAVTAL LWMEIGISCL AG MAVLIIL LPLQSCFGKL FSSLRSKTAT FTDARIRTMN EVITGIRIIK MYAWEKSFSN LITNLRKKEI SKILRSSCLR GMN LASFFS ASKIIVFVTF TTYVLLGSVI TASRVFVAVT LYGAVRLTVT LFFPSAIERV SEAIVSIRRI QTFLLLDEIS QRNR QLPSD GKKMVHVQDF TAFWDKASET PTLQGLSFTV RPGELLAVVG PVGAGKSSLL SAVLGELAPS HGLVSVHGRI AYVSQ QPWV FSGTLRSNIL FGKKYEKERY EKVIKACALK KDLQLLEDGD LTVIGDRGTT LSGGQKARVN LARAVYQDAD IYLLDD PLS AVDAEVSRHL FELCICQILH EKITILVTHQ LQYLKAASQI LILKDGKMVQ KGTYTEFLKS GIDFGSLLKK DNEESEQ PP VPGTPTLRNR TFSESSVWSQ QSSRPSLKDG ALESQDTENV PVTLSEENRS EGKVGFQAYK NYFRAGAHWI VFIFLILL N TAAQVAYVLQ DWWLSYWANK QSMLNVTVNG GGNVTEKLDL NWYLGIYSGL TVATVLFGIA RSLLVFYVLV NSSQTLHNK MFESILKAPV LFFDRNPIGR ILNRFSKDIG HLDDLLPLTF LDFIQTLLQV VGVVSVAVAV IPWIAIPLVP LGIIFIFLRR YFLETSRDV KRLESTTRSP VFSHLSSSLQ GLWTIRAYKA EERCQELFDA HQDLHSEAWF LFLTTSRWFA VRLDAICAMF V IIVAFGSL ILAKTLDAGQ VGLALSYALT LMGMFQWCVR QSAEVENMMI SVERVIEYTD LEKEAPWEYQ KRPPPAWPHE GV IIFDNVN FMYSPGGPLV LKHLTALIKS QEKVGIVGRT GAGKSSLISA LFRLSEPEGK IWIDKILTTE IGLHDLRKKM SII PQEPVL FTGTMRKNLD PFNEHTDEEL WNALQEVQLK ETIEDLPGKM DTELAESGSN FSVGQRQLVC LARAILRKNQ ILII DEATA NVDPRTDELI QKKIREKFAH CTVLTIAHRL NTIIDSDKIM VLDSGRLKEY DEPYVLLQNK ESLFYKMVQQ LGKAE AAAL TETAKQVYFK RNYPHIGHTD HMVTNTSNGQ PSTLTIFETA L UniProtKB: ATP-binding cassette sub-family C member 4 |
-Macromolecule #2: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13...
Macromolecule | Name: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-oxane]-16-yl]oxyethyl]propane-1,3-diol type: ligand / ID: 2 / Number of copies: 14 / Formula: DU0 |
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Molecular weight | Theoretical: 516.752 Da |
Chemical component information | ![]() ChemComp-DU0: |
-Macromolecule #3: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 3 / Number of copies: 1 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.5 / Component - Concentration: 25.0 mM / Component - Name: Hepes Details: 50 mM HEPES pH 7.5, 150 mM NaCl, 2 mM DTT, 2 mM MgCl2, 0.005% (w/v) GDN and 0.0005% CHS |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: After incubation on the grids at 277K under 100% humidity for 10 s, the grids were bloted for 3.0 s and then plunged frozen into liquid ethane cooled by liquid nitrogen using a Vitrobot.. |
Details | The human ABCC4 protein was purified in 0.005% (w/v) GDN and 0.0005% CHS, the peak protein fraction from gel filtration column were concentrated to about 10 mg/ml. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.1 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-8xok: |