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Open data
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Basic information
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Title | Cryo EM structure of lysosomal ATPase | |||||||||
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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 / P-type ion transporter activity / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy ...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 / P-type ion transporter activity / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy / negative regulation of lysosomal protein catabolic process / regulation of lysosomal protein catabolic process / autophagosome-lysosome fusion / regulation of autophagy of mitochondrion / intracellular monoatomic cation homeostasis / autophagosome organization / protein localization to lysosome / phosphatidic acid binding / multivesicular body membrane / positive regulation of exosomal secretion / ATPase-coupled monoatomic cation transmembrane transporter activity / intracellular zinc ion homeostasis / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / regulation of protein localization to nucleus / cupric ion binding / regulation of mitochondrion organization / regulation of endopeptidase activity / phosphatidylinositol-3,5-bisphosphate binding / cellular response to zinc ion / lysosomal transport / regulation of intracellular protein transport / lipid homeostasis / autophagosome membrane / Ion transport by P-type ATPases / autophagosome / regulation of macroautophagy / cellular response to manganese ion / regulation of neuron apoptotic process / transport vesicle / monoatomic ion transmembrane transport / multivesicular body / lysosomal lumen / positive regulation of protein secretion / transmembrane transport / autophagy / intracellular calcium ion homeostasis / late endosome / late endosome membrane / manganese ion binding / cellular response to oxidative stress / intracellular iron ion homeostasis / vesicle / protein autophosphorylation / lysosome / neuron projection / lysosomal membrane / neuronal cell body / positive regulation of gene expression / ATP hydrolysis activity / zinc ion binding / ATP binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Zhang SS | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2. Authors: Xudong Chen / Mingze Zhou / Sensen Zhang / Jian Yin / Ping Zhang / Xujun Xuan / Peiyi Wang / Zhiqiang Liu / Boda Zhou / Maojun Yang / ![]() Abstract: Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal ...Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.8 KB 10.8 KB | Display Display | ![]() |
Images | ![]() | 39.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 339.7 KB | Display | ![]() |
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Full document | ![]() | 339.3 KB | Display | |
Data in XML | ![]() | 5.7 KB | Display | |
Data in CIF | ![]() | 6.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7fjpMC ![]() 7fjmC ![]() 7fjqC 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: 1.0979 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : lysosomal ATPase E1p_ADP
Entire | Name: lysosomal ATPase E1p_ADP |
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Components |
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-Supramolecule #1: lysosomal ATPase E1p_ADP
Supramolecule | Name: lysosomal ATPase E1p_ADP / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | 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: 125.239844 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSADSSPLVG STPTGYGTLT IGTSIDPLSS SVSSVRLSGY CGSPWRVIGY HVVVWMMAGI PLLLFRWKPL WGVRLRLRPC NLAHAETLV IEIRDKEDSS WQLFTVQVQT EAIGEGSLEP SPQSQAEDGR SQAAVGAVPE GAWKDTALHK SEEAVSVGQK R VLRYYLFQ ...String: MSADSSPLVG STPTGYGTLT IGTSIDPLSS SVSSVRLSGY CGSPWRVIGY HVVVWMMAGI PLLLFRWKPL WGVRLRLRPC NLAHAETLV IEIRDKEDSS WQLFTVQVQT EAIGEGSLEP SPQSQAEDGR SQAAVGAVPE GAWKDTALHK SEEAVSVGQK R VLRYYLFQ GQRYIWIETQ QAFYQVSLLD HGRSCDDVHR SRHGLSLQDQ MVRKAIYGPN VISIPVKSYP QLLVDEALNP YY GFQAFSI ALWLADHYYW YALCIFLISS ISICLSLYKT RKQSQTLRDM VKLSMRVCVC RPGGEEEWVD SSELVPGDCL VLP QEGGLM PCDAALVAGE CMVNESSLTG ESIPVLKTAL PEGLGPYCAE THRRHTLFCG TLILQARAYV GPHVLAVVTR TGFC TAKGG LVSSILHPRP INFKFYKHSM KFVAALSVLA LLGTIYSIFI LYRNRVPLNE IVIRALDLVT VVVPPALPAA MTVCT LYAQ SRLRRQGIFC IHPLRINLGG KLQLVCFDKT GTLTEDGLDV MGVVPLKGQA FLPLVPEPRR LPVGPLLRAL ATCHAL SRL QDTPVGDPMD LKMVESTGPQ LQAMEEPPVP VSVLHRFPFS SALQRMSVVV AWPGATQPEA YVKGSPELVA GLCNPET VP TDFAQMLQSY TAAGYRVVAL ASKPLPTVPS LEAAQQLTRD TVEGDLSLLG LLVMRNLLKP QTTPVIQALR RTRIRAVM V TGDNLQTAVT VARGCGMVAP QEHLIIVHAT GQPASLEFLP MESPTAVNGV KDPDQAASYT VEPDPRSRHL ALSGPTFGI IVKHFPKLLP KVLVQGTVFA RMAPEQKTEL VCELQKLQYC VGMCGDGAND CGALKAADVG ISLSQAEASV VSPFTSSMAS IECVPMVIR EGRCSLDTSF SVFKYMALYS LTQFISVLIL YTINTNLGDL QFLAIDLVIT TTVAVLMSRT GPALVLGRVR P PGALLSVP VLSSLLLQMV LVTGVQLGGY FLTLAQPWFV PLNRTVAAPD NLPNYENTVV FSLSSFQYLI LAAAVSKGAP FR RPLYTNV PFLVALALLS SVLVGLVLVP GLLQGPLALR NITDTGFKLL LLGLVTLNFV GAFMLESVLD QCLPACLRRL RPK RASKKR FKQLERELAE QPWPPLPAGP LR |
-Macromolecule #2: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 2 / Number of copies: 1 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ![]() ChemComp-PO4: |
-Macromolecule #3: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ![]() ChemComp-ADP: |
-Macromolecule #4: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 4 / 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: 7.2 |
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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: GATAN K2 SUMMIT (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 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 317000 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |