+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31627 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo EM structure of lysosomal ATPase | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Function / homology | Function and homology information polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / P-type ion transporter activity / regulation of chaperone-mediated autophagy ...polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / P-type ion transporter activity / 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 / lysosomal transport / regulation of endopeptidase activity / regulation of mitochondrion organization / phosphatidylinositol-3,5-bisphosphate binding / cellular response to zinc ion / regulation of intracellular protein transport / lipid homeostasis / Ion transport by P-type ATPases / autophagosome membrane / cellular response to manganese ion / regulation of macroautophagy / regulation of neuron apoptotic process / transport vesicle / autophagosome / multivesicular body / lysosomal lumen / positive regulation of protein secretion / transmembrane transport / autophagy / intracellular calcium ion homeostasis / late endosome / monoatomic ion transmembrane transport / 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: 3.6 Å | |||||||||
Authors | Zhang SS | |||||||||
Funding support | China, 1 items
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_31627.map.gz | 49.6 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-31627-v30.xml emd-31627.xml | 10.1 KB 10.1 KB | Display Display | EMDB header |
Images | emd_31627.png | 38.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31627 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31627 | HTTPS FTP |
-Validation report
Summary document | emd_31627_validation.pdf.gz | 397.5 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_31627_full_validation.pdf.gz | 397 KB | Display | |
Data in XML | emd_31627_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_31627_validation.cif.gz | 7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31627 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31627 | HTTPS FTP |
-Related structure data
Related structure data | 7fjqMC 7fjmC 7fjpC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_31627.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0979 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Sample components
-Entire : Lysosomal ATPase E2Pi state
Entire | Name: Lysosomal ATPase E2Pi state |
---|---|
Components |
|
-Supramolecule #1: Lysosomal ATPase E2Pi state
Supramolecule | Name: Lysosomal ATPase E2Pi state / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
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 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 125.889555 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 THPERGQPAS LEFLPMESPT AVNGVKDPDQ AASYTVEPDP RSRHLALSG PTFGIIVKHF PKLLPKVLVQ GTVFARMAPE QKTELVCELQ KLQYCVGMCG DGANDCGALK AADVGISLSQ AEASVVSPFT SSMASIECV PMVIREGRCS LDTSFSVFKY MALYSLTQFI SVLILYTINT NLGDLQFLAI DLVITTTVAV LMSRTGPALV L GRVRPPGA LLSVPVLSSL LLQMVLVTGV QLGGYFLTLA QPWFVPLNRT VAAPDNLPNY ENTVVFSLSS FQYLILAAAV SK GAPFRRP LYTNVPFLVA LALLSSVLVG LVLVPGLLQG PLALRNITDT GFKLLLLGLV TLNFVGAFML ESVLDQCLPA CLR RLRPKR ASKKRFKQLE RELAEQPWPP LPAGPLR |
-Macromolecule #2: SPERMINE
Macromolecule | Name: SPERMINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: SPM |
---|---|
Molecular weight | Theoretical: 202.34 Da |
Chemical component information | ChemComp-SPM: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 256000 |
---|---|
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |