+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31623 | |||||||||
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Title | Cryo EM structure of lysosomal ATPase | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / polyamine transmembrane transporter activity / ABC-type polyamine transporter activity / regulation of autophagosome size / P-type ion transporter activity / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy ...polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / polyamine transmembrane transporter activity / ABC-type polyamine 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 autophagy of mitochondrion / regulation of lysosomal protein catabolic process / autophagosome-lysosome fusion / intracellular monoatomic cation homeostasis / autophagosome organization / protein localization to lysosome / phosphatidic acid binding / positive regulation of exosomal secretion / multivesicular body membrane / 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 endopeptidase activity / regulation of mitochondrion organization / phosphatidylinositol-3,5-bisphosphate binding / lysosomal transport / cellular response to zinc ion / regulation of intracellular protein transport / lipid homeostasis / Ion transport by P-type ATPases / autophagosome membrane / regulation of macroautophagy / cellular response to manganese ion / regulation of neuron apoptotic process / transport vesicle / autophagosome / multivesicular body / lysosomal lumen / positive regulation of protein secretion / transmembrane transport / autophagy / intracellular calcium ion homeostasis / monoatomic ion transmembrane transport / 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 | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Zhang SS | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Discov / Year: 2021 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 | emd_31623.map.gz | 49.7 MB | EMDB map data format | |
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Header (meta data) | emd-31623-v30.xml emd-31623.xml | 9.7 KB 9.7 KB | Display Display | EMDB header |
Images | emd_31623.png | 45.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31623 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31623 | HTTPS FTP |
-Validation report
Summary document | emd_31623_validation.pdf.gz | 416.7 KB | Display | EMDB validaton report |
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Full document | emd_31623_full_validation.pdf.gz | 416.2 KB | Display | |
Data in XML | emd_31623_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_31623_validation.cif.gz | 7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31623 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31623 | HTTPS FTP |
-Related structure data
Related structure data | 7fjmMC 7fjpC 7fjqC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31623.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
-Sample components
-Entire : plasma membaren channel
Entire | Name: plasma membaren channel |
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Components |
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-Supramolecule #1: plasma membaren channel
Supramolecule | Name: plasma membaren channel / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 125.367961 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSADSSPLVG STPTGYGTLT IGTSIDPLSS SVSSVRLSGY CGSPWRVIGY HVVVWMMAGI PLLLFRWKPL WGVRLRLRPC NLAHAETLV IEIRDKEDSS WQLFTVQVQT EAIGEGSLEP SPQSQAEDGR SQAAVGAVPE GAWKDTAQLH KSEEAVSVGQ K RVLRYYLF ...String: MSADSSPLVG STPTGYGTLT IGTSIDPLSS SVSSVRLSGY CGSPWRVIGY HVVVWMMAGI PLLLFRWKPL WGVRLRLRPC NLAHAETLV IEIRDKEDSS WQLFTVQVQT EAIGEGSLEP SPQSQAEDGR SQAAVGAVPE GAWKDTAQLH KSEEAVSVGQ K RVLRYYLF QGQRYIWIET QQAFYQVSLL DHGRSCDDVH RSRHGLSLQD QMVRKAIYGP NVISIPVKSY PQLLVDEALN PY YGFQAFS IALWLADHYY WYALCIFLIS SISICLSLYK TRKQSQTLRD MVKLSMRVCV CRPGGEEEWV DSSELVPGDC LVL PQEGGL MPCDAALVAG ECMVNESSLT GESIPVLKTA LPEGLGPYCA ETHRRHTLFC GTLILQARAY VGPHVLAVVT RTGF CTAKG GLVSSILHPR PINFKFYKHS MKFVAALSVL ALLGTIYSIF ILYRNRVPLN EIVIRALDLV TVVVPPALPA AMTVC TLYA QSRLRRQGIF CIHPLRINLG GKLQLVCFDK TGTLTEDGLD VMGVVPLKGQ AFLPLVPEPR RLPVGPLLRA LATCHA LSR LQDTPVGDPM DLKMVESTGP QLQAMEEPPV PVSVLHRFPF SSALQRMSVV VAWPGATQPE AYVKGSPELV AGLCNPE TV PTDFAQMLQS YTAAGYRVVA LASKPLPTVP SLEAAQQLTR DTVEGDLSLL GLLVMRNLLK PQTTPVIQAL RRTRIRAV M VTGDNLQTAV TVARGCGMVA PQEHLIIVHA TGQPASLEFL PMESPTAVNG VKDPDQAASY TVEPDPRSRH LALSGPTFG IIVKHFPKLL PKVLVQGTVF ARMAPEQKTE LVCELQKLQY CVGMCGDGAN DCGALKAADV GISLSQAEAS VVSPFTSSMA SIECVPMVI REGRCSLDTS FSVFKYMALY SLTQFISVLI LYTINTNLGD LQFLAIDLVI TTTVAVLMSR TGPALVLGRV R PPGALLSV PVLSSLLLQM VLVTGVQLGG YFLTLAQPWF VPLNRTVAAP DNLPNYENTV VFSLSSFQYL ILAAAVSKGA PF RRPLYTN VPFLVALALL SSVLVGLVLV PGLLQGPLAL RNITDTGFKL LLLGLVTLNF VGAFMLESVL DQCLPACLRR LRP KRASKK RFKQLERELA EQPWPPLPAG PLR |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 153193 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |