+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38065 | |||||||||
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Title | Cryo-EM structures of human XPR1 in closed states | |||||||||
Map data | main map | |||||||||
Sample |
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Keywords | transport / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information phosphate transmembrane transporter activity / phosphate ion transport / intracellular phosphate ion homeostasis / inositol hexakisphosphate binding / phosphate ion transmembrane transport / cellular response to phosphate starvation / efflux transmembrane transporter activity / response to virus / virus receptor activity / Golgi apparatus ...phosphate transmembrane transporter activity / phosphate ion transport / intracellular phosphate ion homeostasis / inositol hexakisphosphate binding / phosphate ion transmembrane transport / cellular response to phosphate starvation / efflux transmembrane transporter activity / response to virus / virus receptor activity / Golgi apparatus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.84 Å | |||||||||
Authors | Jiang DH / Yan R | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2024 Title: Human XPR1 structures reveal phosphate export mechanism. Authors: Rui Yan / Huiwen Chen / Chuanyu Liu / Jun Zhao / Di Wu / Juquan Jiang / Jianke Gong / Daohua Jiang / Abstract: Inorganic phosphate (Pi) is a fundamental macronutrient for all living organisms, the homeostasis of which is critical for numerous biological activities. As the only known human Pi exporter to date, ...Inorganic phosphate (Pi) is a fundamental macronutrient for all living organisms, the homeostasis of which is critical for numerous biological activities. As the only known human Pi exporter to date, XPR1 has an indispensable role in cellular Pi homeostasis. Dysfunction of XPR1 is associated with neurodegenerative disease. However, the mechanisms underpinning XPR1-mediated Pi efflux and regulation by the intracellular inositol polyphosphate (InsPP) sensor SPX domain remain poorly understood. Here we present cryo-electron microscopy structures of human XPR1 in Pi-bound closed, open and InsP-bound forms, revealing the structural basis for XPR1 gating and regulation by InsPPs. XPR1 consists of an N-terminal SPX domain, a dimer-formation core domain and a Pi transport domain. Within the transport domain, three basic clusters are responsible for Pi binding and transport, and a conserved W573 acts as a molecular switch for gating. In addition, the SPX domain binds to InsP and facilitates Pi efflux by liberating the C-terminal loop that limits Pi entry. This study provides a conceptual framework for the mechanistic understanding of Pi homeostasis by XPR1 homologues in fungi, plants and animals. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38065.map.gz | 117.8 MB | EMDB map data format | |
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Header (meta data) | emd-38065-v30.xml emd-38065.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
Images | emd_38065.png | 74.1 KB | ||
Filedesc metadata | emd-38065.cif.gz | 5.6 KB | ||
Others | emd_38065_half_map_1.map.gz emd_38065_half_map_2.map.gz | 115.9 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38065 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38065 | HTTPS FTP |
-Validation report
Summary document | emd_38065_validation.pdf.gz | 978.4 KB | Display | EMDB validaton report |
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Full document | emd_38065_full_validation.pdf.gz | 978 KB | Display | |
Data in XML | emd_38065_validation.xml.gz | 14 KB | Display | |
Data in CIF | emd_38065_validation.cif.gz | 16.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38065 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38065 | HTTPS FTP |
-Related structure data
Related structure data | 8x5bMC 8x5eC 8x5fC 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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-Map
File | Download / File: emd_38065.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | main map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map
File | emd_38065_half_map_1.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map
File | emd_38065_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : transport
Entire | Name: transport |
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Components |
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-Supramolecule #1: transport
Supramolecule | Name: transport / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Solute carrier family 53 member 1
Macromolecule | Name: Solute carrier family 53 member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 54.831422 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: APAWTTFRVG LFCGIFIVLN ITLVLAAVFK LETDRSIWPL IRIYRGGFLL IEFLFLLGIN TYGWRQAGVN HVLIFELNPR SNLSHQHLF EIAGFLGILW CLSLLACFFA PISVIPTYVY PLALYGFMVF FLINPTKTFY YKSRFWLLKL LFRVFTAPFH K VGFADFWL ...String: APAWTTFRVG LFCGIFIVLN ITLVLAAVFK LETDRSIWPL IRIYRGGFLL IEFLFLLGIN TYGWRQAGVN HVLIFELNPR SNLSHQHLF EIAGFLGILW CLSLLACFFA PISVIPTYVY PLALYGFMVF FLINPTKTFY YKSRFWLLKL LFRVFTAPFH K VGFADFWL ADQLNSLSVI LMDLEYMICF YSLELKWDES KGLLPNNSEE SGICHKYTYG VRAIVQCIPA WLRFIQCLRR YR DTKRAFP HLVNAGKYST TFFMVTFAAL YSTHKERGHS DTMVFFYLWI VFYIISSCYT LIWDLKMDWG LFDKNAGENT FLR EEIVYP QKAYYYCAII EDVILRFAWT IQISITSTTL LPHSGDIIAT VFAPLEVFRR FVWNFFRLEN EHLNNCGEFR AVRD ISVAP LNADDQTLLE QMMDQDDGVR NRQKNRSWKY NQSISLRRPR LASQSKARDT KVLIEDTDDE ANT UniProtKB: Solute carrier family 53 member 1 |
-Macromolecule #2: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 2 / Number of copies: 8 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ChemComp-PO4: |
-Macromolecule #3: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 3 / Number of copies: 18 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #4: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 14 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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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 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 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: 2.0 µm / Nominal defocus min: 1.0 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: 2.84 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 253874 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |