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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-32066 | ||||||||||||
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Title | Cryo-EM structure of the human ATP13A2 (E1-ATP state) | ||||||||||||
![]() | postprocess_masked.mrc from Relion | ||||||||||||
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Function / homology | ![]() ABC-type polyamine transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / polyamine transmembrane transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Tomita A / Yamashita K / Nishizawa T / Nureki O | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2. Authors: Atsuhiro Tomita / Takashi Daiho / Tsukasa Kusakizako / Keitaro Yamashita / Satoshi Ogasawara / Takeshi Murata / Tomohiro Nishizawa / Osamu Nureki / ![]() ![]() Abstract: The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine ...The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer's disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ATP13A2 under four different conditions, revealing the structural coupling between the polyamine binding and the dephosphorylation. Polyamine is bound at the luminal tunnel and recognized through numerous electrostatic and π-cation interactions, explaining its broad specificity. The unique N-terminal domain is anchored to the lipid membrane to stabilize the E2P conformation, thereby accelerating the E1P-to-E2P transition. These findings reveal the distinct mechanism of P5B ATPases, thereby paving the way for neuroprotective therapy by activating ATP13A2. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18 KB 18 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 5.1 KB | Display | ![]() |
Images | ![]() | 125.1 KB | ||
Masks | ![]() | 6.3 MB | ![]() | |
Others | ![]() ![]() | 5.4 MB 5.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vpiMC ![]() 7vpjC ![]() 7vpkC ![]() 7vplC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Unaligned movies for E1-ATP state [micrographs - multiframe] Data #2: Unaligned movies for E1P-ADP state [micrographs - multiframe] Data #3: Unaligned movies for SPM-bound E2P state [micrographs - multiframe] Data #4: Unaligned movies for SPM-bound E2Pi state [micrographs - multiframe]) |
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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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Annotation | postprocess_masked.mrc from Relion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.51771 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: run half1 class001.mrc
File | emd_32066_half_map_1.map | ||||||||||||
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Annotation | run_half1_class001.mrc | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: run half2 class001.mrc
File | emd_32066_half_map_2.map | ||||||||||||
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Annotation | run_half2_class001.mrc | ||||||||||||
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Density Histograms |
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Sample components
-Entire : ATP13A2
Entire | Name: ATP13A2![]() |
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Components |
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-Supramolecule #1: ATP13A2
Supramolecule | Name: ATP13A2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: Human ATP13A2 in complex with AMPPCP |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Polyamine-transporting ATPase 13A2
Macromolecule | Name: Polyamine-transporting ATPase 13A2 / type: protein_or_peptide / ID: 1 / 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: 129.313391 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GPSRMSADSS PLVGSTPTGY GTLTIGTSID PLSSSVSSVR LSGYCGSPWR VIGYHVVVWM MAGIPLLLFR WKPLWGVRLR LRPCNLAHA ETLVIEIRDK EDSSWQLFTV QVQTEAIGEG SLEPSPQSQA EDGRSQAAVG AVPEGAWKDT AQLHKSEEAV S VGQKRVLR ...String: GPSRMSADSS PLVGSTPTGY GTLTIGTSID PLSSSVSSVR LSGYCGSPWR VIGYHVVVWM MAGIPLLLFR WKPLWGVRLR LRPCNLAHA ETLVIEIRDK EDSSWQLFTV QVQTEAIGEG SLEPSPQSQA EDGRSQAAVG AVPEGAWKDT AQLHKSEEAV S VGQKRVLR YYLFQGQRYI WIETQQAFYQ VSLLDHGRSC DDVHRSRHGL SLQDQMVRKA IYGPNVISIP VKSYPQLLVD EA LNPYYGF QAFSIALWLA DHYYWYALCI FLISSISICL SLYKTRKQSQ TLRDMVKLSM RVCVCRPGGE EEWVDSSELV PGD CLVLPQ EGGLMPCDAA LVAGECMVNE SSLTGESIPV LKTALPEGLG PYCAETHRRH TLFCGTLILQ ARAYVGPHVL AVVT RTGFC TAKGGLVSSI LHPRPINFKF YKHSMKFVAA LSVLALLGTI YSIFILYRNR VPLNEIVIRA LDLVTVVVPP ALPAA MTVC TLYAQSRLRR QGIFCIHPLR INLGGKLQLV CFDKTGTLTE DGLDVMGVVP LKGQAFLPLV PEPRRLPVGP LLRALA TCH ALSRLQDTPV GDPMDLKMVE STGWVLEEEP AADSAFGTQV LAVMRPPLWE PQLQAMEEPP VPVSVLHRFP FSSALQR MS VVVAWPGATQ PEAYVKGSPE LVAGLCNPET VPTDFAQMLQ SYTAAGYRVV ALASKPLPTV PSLEAAQQLT RDTVEGDL S LLGLLVMRNL LKPQTTPVIQ ALRRTRIRAV MVTGDNLQTA VTVARGCGMV APQEHLIIVH ATHPERGQPA SLEFLPMES PTAVNGVKDP DQAASYTVEP DPRSRHLALS GPTFGIIVKH FPKLLPKVLV QGTVFARMAP EQKTELVCEL QKLQYCVGMC GDGANDCGA LKAADVGISL SQAEASVVSP FTSSMASIEC VPMVIREGRC SLDTSFSVFK YMALYSLTQF ISVLILYTIN T NLGDLQFL AIDLVITTTV AVLMSRTGPA LVLGRVRPPG ALLSVPVLSS LLLQMVLVTG VQLGGYFLTL AQPWFVPLNR TV AAPDNLP NYENTVVFSL SSFQYLILAA AVSKGAPFRR PLYTNVPFLV ALALLSSVLV GLVLVPGLLQ GPLALRNITD TGF KLLLLG LVTLNFVGAF MLESVLDQCL PACLRRLRPK RASKKRFKQL ERELAEQPWP PLPAGPLR |
-Macromolecule #2: PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER
Macromolecule | Name: PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / type: ligand / ID: 2 / Number of copies: 1 / Formula: ACP |
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Molecular weight | Theoretical: 505.208 Da |
Chemical component information | ![]() ChemComp-ACP: |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER/RHODIUM / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-7vpi: |