+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35386 | |||||||||
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Title | Cryo-EM structure of ATP13A2 in the E2P state | |||||||||
Map data | Cryo-EM structure of ATP13A2 in the E2P state | |||||||||
Sample |
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Keywords | Cryo-EM structure of ATP13A2 in the E2P state / Membran protein / PROTEIN TRANSPORT | |||||||||
Function / homology | Function and homology information 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 / intracellular monoatomic cation homeostasis / autophagosome-lysosome fusion / 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 / 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 | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.35 Å | |||||||||
Authors | Liu ZM / Mu JQ / Xue CY | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2023 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 | emd_35386.map.gz | 86.1 MB | EMDB map data format | |
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Header (meta data) | emd-35386-v30.xml emd-35386.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
Images | emd_35386.png | 33.7 KB | ||
Filedesc metadata | emd-35386.cif.gz | 6.1 KB | ||
Others | emd_35386_half_map_1.map.gz emd_35386_half_map_2.map.gz | 84.7 MB 84.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35386 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35386 | HTTPS FTP |
-Related structure data
Related structure data | 8iemMC 8iekC 8ielC 8ienC 8ieoC 8ierC 8iesC 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_35386.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Cryo-EM structure of ATP13A2 in the E2P state | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.095 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 E2P state
File | emd_35386_half_map_1.map | ||||||||||||
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Annotation | The half_b map of ATP13A2 in the E2P state | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: The half a map of ATP13A2 in the E2P state
File | emd_35386_half_map_2.map | ||||||||||||
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Annotation | The half_a map of ATP13A2 in the E2P state | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Polyamine-transporting ATPase 13A2
Entire | Name: Polyamine-transporting ATPase 13A2 |
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Components |
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-Supramolecule #1: Polyamine-transporting ATPase 13A2
Supramolecule | Name: Polyamine-transporting ATPase 13A2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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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 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 123.906414 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RLSGYCGSPW RVIGYHVVVW MMAGIPLLLF RWKPLWGVRL RLRPCNLAHA ETLVIEIRDK EDSSWQLFTV QVQTEAIGEG SLEPSPQSQ AEDGRSQAAV GAVPEGAWKD TAQLHKSEEA KRVLRYYLFQ GQRYIWIETQ QAFYQVSLLD HGRSCDDVHR S RHGLSLQD ...String: RLSGYCGSPW RVIGYHVVVW MMAGIPLLLF RWKPLWGVRL RLRPCNLAHA ETLVIEIRDK EDSSWQLFTV QVQTEAIGEG SLEPSPQSQ AEDGRSQAAV GAVPEGAWKD TAQLHKSEEA KRVLRYYLFQ GQRYIWIETQ QAFYQVSLLD HGRSCDDVHR S RHGLSLQD QMVRKAIYGP NVISIPVKSY PQLLVDEALN PYYGFQAFSI ALWLADHYYW YALCIFLISS ISICLSLYKT RK QSQTLRD MVKLSMRVCV CRPGGEEEWV DSSELVPGDC LVLPQEGGLM PCDAALVAGE CMVNESSLTG ESIPVLKTAL PEG LGPYCA ETHRRHTLFC GTLILQARAY VGPHVLAVVT RTGFCTAKGG LVSSILHPRP INFKFYKHSM KFVAALSVLA LLGT IYSIF ILYRNRVPLN EIVIRALDLV TVVVPPALPA AMTVCTLYAQ SRLRRQGIFC IHPLRINLGG KLQLVCFDKT GTLTE DGLD VMGVVPLKGQ AFLPLVPEPR RLPVGPLLRA LATCHALSRL QDTPVGDPMD LKMVESTGWV LEEEPAADSA FGTQVL AVM RPPLWEPQLQ AMEEPPVPVS VLHRFPFSSA LQRMSVVVAW PGATQPEAYV KGSPELVAGL CNPETVPTDF AQMLQSY TA AGYRVVALAS KPLPTVPSLE AAQQLTRDTV EGDLSLLGLL VMRNLLKPQT TPVIQALRRT RIRAVMVTGD NLQTAVTV A RGCGMVAPQE HLIIVHATHP ERGQPASLEF LPMESPTAVN GVKDPDQAAS YTVEPDPRSR HLALSGPTFG IIVKHFPKL LPKVLVQGTV FARMAPEQKT ELVCELQKLQ YCVGMCGDGA NDCGALKAAD VGISLSQAEA SVVSPFTSSM ASIECVPMVI REGRCSLDT SFSVFKYMAL YSLTQFISVL ILYTINTNLG DLQFLAIDLV ITTTVAVLMS RTGPALVLGR VRPPGALLSV P VLSSLLLQ MVLVTGVQLG GYFLTLAQPW FVPLNRTVAA PDNLPNYENT VVFSLSSFQY LILAAAVSKG APFRRPLYTN VP FLVALAL LSSVLVGLVL VPGLLQGPLA LRNITDTGFK LLLLGLVTLN FVGAFMLESV LDQCLPACLR RLRPKRASKK RFK QLEREL AEQ 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: |
-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 |
-Macromolecule #4: BERYLLIUM TRIFLUORIDE ION
Macromolecule | Name: BERYLLIUM TRIFLUORIDE ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: BEF |
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Molecular weight | Theoretical: 66.007 Da |
Chemical component information | ChemComp-BEF: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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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 K3 (6k 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 / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 242437 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |