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Open data
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Basic information
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Title | Cryo-EM structure of ATP13A2 in the putative of E2 state | |||||||||
![]() | Cryo-EM structure of ATP13A2 in the putative of E2 state | |||||||||
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![]() | Cryo-EM structure of ATP13A2 in the putative of E2 state / Membrane protein / TRANSPORT PROTEIN | |||||||||
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 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 / multivesicular body membrane / positive regulation of exosomal secretion / ATPase-coupled monoatomic cation transmembrane transporter activity / intracellular zinc ion homeostasis / regulation of protein localization to nucleus / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / cupric ion binding / regulation of endopeptidase activity / regulation of mitochondrion organization / phosphatidylinositol-3,5-bisphosphate binding / cellular response to zinc ion / lysosomal transport / regulation of intracellular protein transport / lipid homeostasis / Ion transport by P-type ATPases / autophagosome membrane / autophagosome / cellular response to manganese ion / regulation of macroautophagy / regulation of neuron apoptotic process / monoatomic ion transmembrane transport / transport vesicle / 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: 4.87 Å | |||||||||
![]() | Liu ZM / Mu JQ / Xue CY | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Conformational cycle of human polyamine transporter ATP13A2. Authors: Jianqiang Mu / Chenyang Xue / Lei Fu / Zongjun Yu / Minhan Nie / Mengqi Wu / Xinmeng Chen / Kun Liu / Ruiqian Bu / Ying Huang / Baisheng Yang / Jianming Han / Qianru Jiang / Kevin C Chan / ...Authors: Jianqiang Mu / Chenyang Xue / Lei Fu / Zongjun Yu / Minhan Nie / Mengqi Wu / Xinmeng Chen / Kun Liu / Ruiqian Bu / Ying Huang / Baisheng Yang / Jianming Han / Qianru Jiang / Kevin C Chan / Ruhong Zhou / Huilin Li / Ancheng Huang / Yong Wang / Zhongmin Liu / ![]() Abstract: Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a ...Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 96.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.4 KB 15.4 KB | Display Display | ![]() |
Images | ![]() | 40.3 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() | 95.3 MB 95.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ierMC ![]() 8iekC ![]() 8ielC ![]() 8iemC ![]() 8ienC ![]() 8ieoC ![]() 8iesC 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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Annotation | Cryo-EM structure of ATP13A2 in the putative of E2 state | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: The half b map of ATP13A2 in the putative of E2 state
File | emd_35391_half_map_1.map | ||||||||||||
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Annotation | The half_b map of ATP13A2 in the putative of E2 state | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: The half a map of ATP13A2 in the putative of E2 state
File | emd_35391_half_map_2.map | ||||||||||||
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Annotation | The half_a map of ATP13A2 in the putative of E2 state | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Cryo-EM structure of ATP13A2 in the putative of E2 state
Entire | Name: Cryo-EM structure of ATP13A2 in the putative of E2 state |
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Components |
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-Supramolecule #1: Cryo-EM structure of ATP13A2 in the putative of E2 state
Supramolecule | Name: Cryo-EM structure of ATP13A2 in the putative of E2 state type: complex / 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: 128.914984 KDa |
Recombinant expression | Organism: ![]() |
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 DLKMVESTGW VLEEEPAADS AFGTQVLAVM RPPLWEPQLQ AMEEPPVPVS VLHRFPFSSA LQRMSVV VA WPGATQPEAY VKGSPELVAG LCNPETVPTD FAQMLQSYTA AGYRVVALAS KPLPTVPSLE AAQQLTRDTV EGDLSLLG L LVMRNLLKPQ TTPVIQALRR TRIRAVMVTG DNLQTAVTVA RGCGMVAPQE HLIIVHATHP ERGQPASLEF LPMESPTAV NGVKDPDQAA SYTVEPDPRS RHLALSGPTF GIIVKHFPKL LPKVLVQGTV FARMAPEQKT ELVCELQKLQ YCVGMCGDGA NDCGALKAA DVGISLSQAE ASVVSPFTSS MASIECVPMV IREGRCSLDT SFSVFKYMAL YSLTQFISVL ILYTINTNLG D LQFLAIDL VITTTVAVLM SRTGPALVLG RVRPPGALLS VPVLSSLLLQ MVLVTGVQLG GYFLTLAQPW FVPLNRTVAA PD NLPNYEN TVVFSLSSFQ YLILAAAVSK GAPFRRPLYT NVPFLVALAL LSSVLVGLVL VPGLLQGPLA LRNITDTGFK LLL LGLVTL NFVGAFMLES VLDQCLPACL RRLRPKRASK KRFKQLEREL AEQPWPPLPA GPLR UniProtKB: Polyamine-transporting ATPase 13A2 |
-Macromolecule #2: SPERMINE
Macromolecule | Name: SPERMINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: SPM |
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Molecular weight | Theoretical: 202.34 Da |
Chemical component information | ![]() ChemComp-SPM: |
-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 |
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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 K3 (6k 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: DARK FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.87 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 394767 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |