+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17192 | |||||||||
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Title | Complex of human ASCT2 with Syncytin-1 | |||||||||
Map data | 2.62 Ang map of ASCT2-Syncytin-1. | |||||||||
Sample |
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Keywords | Small neutral amino acid transporter / ASCT2 / Syncytin-1 / Receptor binding domain / PROTEIN TRANSPORT | |||||||||
Function / homology | Function and homology information syncytium formation by plasma membrane fusion / glutamine secretion / syncytium formation / L-glutamine import across plasma membrane / glutamine transport / L-glutamine transmembrane transporter activity / L-serine transmembrane transporter activity / ligand-gated channel activity / neutral amino acid transport / amino acid transmembrane transporter activity ...syncytium formation by plasma membrane fusion / glutamine secretion / syncytium formation / L-glutamine import across plasma membrane / glutamine transport / L-glutamine transmembrane transporter activity / L-serine transmembrane transporter activity / ligand-gated channel activity / neutral amino acid transport / amino acid transmembrane transporter activity / Amino acid transport across the plasma membrane / L-aspartate transmembrane transporter activity / L-aspartate import across plasma membrane / neutral L-amino acid transmembrane transporter activity / symporter activity / myoblast fusion / antiporter activity / amino acid transport / RHOJ GTPase cycle / RHOQ GTPase cycle / protein homotrimerization / RHOH GTPase cycle / transport across blood-brain barrier / anatomical structure morphogenesis / RAC3 GTPase cycle / RAC1 GTPase cycle / erythrocyte differentiation / basal plasma membrane / melanosome / virus receptor activity / signaling receptor activity / extracellular exosome / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.62 Å | |||||||||
Authors | Khare S / Reyes N | |||||||||
Funding support | European Union, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Receptor-recognition and antiviral mechanisms of retrovirus-derived human proteins. Authors: Shashank Khare / Miryam I Villalba / Juan C Canul-Tec / Arantza Balsebre Cajiao / Anand Kumar / Marija Backovic / Felix A Rey / Els Pardon / Jan Steyaert / Camilo Perez / Nicolas Reyes / Abstract: Human syncytin-1 and suppressyn are cellular proteins of retroviral origin involved in cell-cell fusion events to establish the maternal-fetal interface in the placenta. In cell culture, they ...Human syncytin-1 and suppressyn are cellular proteins of retroviral origin involved in cell-cell fusion events to establish the maternal-fetal interface in the placenta. In cell culture, they restrict infections from members of the largest interference group of vertebrate retroviruses, and are regarded as host immunity factors expressed during development. At the core of the syncytin-1 and suppressyn functions are poorly understood mechanisms to recognize a common cellular receptor, the membrane transporter ASCT2. Here, we present cryo-electron microscopy structures of human ASCT2 in complexes with the receptor-binding domains of syncytin-1 and suppressyn. Despite their evolutionary divergence, the two placental proteins occupy similar positions in ASCT2, and are stabilized by the formation of a hybrid β-sheet or 'clamp' with the receptor. Structural predictions of the receptor-binding domains of extant retroviruses indicate overlapping binding interfaces and clamping sites with ASCT2, revealing a competition mechanism between the placental proteins and the retroviruses. Our work uncovers a common ASCT2 recognition mechanism by a large group of endogenous and disease-causing retroviruses, and provides high-resolution views on how placental human proteins exert morphological and immunological functions. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_17192.map.gz | 122.1 MB | EMDB map data format | |
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Header (meta data) | emd-17192-v30.xml emd-17192.xml | 22.1 KB 22.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17192_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_17192.png | 116.8 KB | ||
Filedesc metadata | emd-17192.cif.gz | 7 KB | ||
Others | emd_17192_half_map_1.map.gz emd_17192_half_map_2.map.gz | 226.8 MB 226.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17192 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17192 | HTTPS FTP |
-Related structure data
Related structure data | 8ouhMC 8oudC 8ouiC 8oujC 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_17192.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | 2.62 Ang map of ASCT2-Syncytin-1. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.731 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_17192_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17192_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of ASCT2 with Synctin-1
Entire | Name: Complex of ASCT2 with Synctin-1 |
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Components |
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-Supramolecule #1: Complex of ASCT2 with Synctin-1
Supramolecule | Name: Complex of ASCT2 with Synctin-1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Molecular weight | Theoretical: 180 kDa/nm |
-Supramolecule #2: Alanine Serine Cysteine Transporter 2
Supramolecule | Name: Alanine Serine Cysteine Transporter 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Syncytin-1
Supramolecule | Name: Syncytin-1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Neutral amino acid transporter B(0)
Macromolecule | Name: Neutral amino acid transporter B(0) / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 58.984566 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MWSHPQFEKS SGGLEVLFQG PMVADPPRDS KGLAAAEPTA NGGLALASIE DQGAAAGGYC GSRDQVRRCL RANLLVLLTV VAVVAGVAL GLGVSGAGGA LALGPERLSA FVFPGELLLR LLRMIILPLV VCSLIGGAAS LDPGALGRLG AWALLFFLVT T LLASALGV ...String: MWSHPQFEKS SGGLEVLFQG PMVADPPRDS KGLAAAEPTA NGGLALASIE DQGAAAGGYC GSRDQVRRCL RANLLVLLTV VAVVAGVAL GLGVSGAGGA LALGPERLSA FVFPGELLLR LLRMIILPLV VCSLIGGAAS LDPGALGRLG AWALLFFLVT T LLASALGV GLALALQPGA ASAAINASVG AAGSAENAPS KEVLDSFLDL ARNIFPSNLV SAAFRSYSTT YEERNITGTR VK VPVGQEV EGMNILGLVV FAIVFGVALR KLGPEGELLI RFFNSFNEAT MVLVSWIMWY APVGIMFLVA GKIVEMEDVG LLF ARLGKY ILCCLLGHAI HGLLVLPLIY FLFTRKNPYR FLWGIVTPLA TAFGTSSSSA TLPLMMKCVE ENNGVAKHIS RFIL PIGAT VNMDGAALFQ CVAAVFIAQL SQQSLDFVKI ITILVTATAS SVGAAGIPAG GVLTLAIILE AVNLPVDHIS LILAV DWLV DRSCTVLNVE GDALGAGLLQ NYVDRTESRS TEPELIQVKS ELPLDPLPVP TEEGNPLLKH YRGPAGDATV ASEKES VM UniProtKB: Neutral amino acid transporter B(0) |
-Macromolecule #2: Syncytin-1
Macromolecule | Name: Syncytin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.24593 KDa |
Recombinant expression | Organism: Drosophila melanogaster (fruit fly) |
Sequence | String: AVVAFVGLSL GAPPPCRCMT SSSPYQEFLW RMQRPGNIDA PSYRSLSKGT PTFTAHTHMP RNCYHSATLC MHANTHYWTG KMINPSCPG GLGVTVCWTY FTQTGMSDGG GVQDQAREKH VKEVISQLTR VHGTSSPYKG LDLSKLHETL RTHTRLVSLF N TTLTGLHE ...String: AVVAFVGLSL GAPPPCRCMT SSSPYQEFLW RMQRPGNIDA PSYRSLSKGT PTFTAHTHMP RNCYHSATLC MHANTHYWTG KMINPSCPG GLGVTVCWTY FTQTGMSDGG GVQDQAREKH VKEVISQLTR VHGTSSPYKG LDLSKLHETL RTHTRLVSLF N TTLTGLHE VSAQNPTNSW ICLPLNFRPY VSIPVPEQWN NFSTEINTTS VLVGPLVSNL EITHTSNLTC VKFSNTTYTT NS QCIRWVT PPTQIVCLPS GIFFVCGTSA YRCLNGSSES MCFLSFLVPP MTIYTEQDLY NYVISKPRNK RVPILPFVIG AGV LGALGT GIGGITTSTQ FYYKLSQELN GDMERVADSL VTLQDQLNSL AAVVLQNRRA LDLLTAERGG TCLFLGEECC YYVN QSGIV TEKVKEIRDR IQRRAEELRN TGPWGSGLEV LFQGPGPEPE A UniProtKB: Syncytin-1 |
-Macromolecule #3: ALANINE
Macromolecule | Name: ALANINE / type: ligand / ID: 3 / Number of copies: 2 / Formula: ALA |
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Molecular weight | Theoretical: 89.093 Da |
Chemical component information | ChemComp-ALA: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 9 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 10 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.003 kPa | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.4 µm / Nominal magnification: 165000 |
Specialist optics | Phase plate: VOLTA PHASE PLATE / Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV |
Sample stage | Cooling holder cryogen: NITROGEN |
Software | Name: EPU (ver. 2) |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 15376 / Average exposure time: 6.0 sec. / Average electron dose: 53.4 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Initial model |
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Software | Name: Coot (ver. 0.9.8.3) | |||||||||
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 60.1 | |||||||||
Output model | PDB-8ouh: |