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- EMDB-17192: Complex of human ASCT2 with Syncytin-1 -

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Basic information

Entry
Database: EMDB / ID: EMD-17192
TitleComplex of human ASCT2 with Syncytin-1
Map data2.62 Ang map of ASCT2-Syncytin-1.
Sample
  • Complex: Complex of ASCT2 with Synctin-1
    • Complex: Alanine Serine Cysteine Transporter 2
      • Protein or peptide: Neutral amino acid transporter B(0)
    • Complex: Syncytin-1
      • Protein or peptide: Syncytin-1
  • Ligand: ALANINE
KeywordsSmall 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 / neutral L-amino acid transmembrane transporter activity / L-aspartate transmembrane transporter activity / L-aspartate import across plasma membrane / symporter activity / myoblast fusion / amino acid transport / antiporter activity / 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 / basal plasma membrane / erythrocyte differentiation / melanosome / virus receptor activity / signaling receptor activity / extracellular exosome / membrane / metal ion binding / plasma membrane
Similarity search - Function
ENV polyprotein (coat polyprotein) / TLV/ENV coat polyprotein / Sodium:dicarboxylate symporter family signature 2. / Sodium:dicarboxylate symporter / Sodium:dicarboxylate symporter, conserved site / Sodium:dicarboxylate symporter superfamily / Sodium:dicarboxylate symporter family / Sodium:dicarboxylate symporter family signature 1.
Similarity search - Domain/homology
Neutral amino acid transporter B(0) / Syncytin-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.62 Å
AuthorsKhare S / Reyes N
Funding supportEuropean Union, 1 items
OrganizationGrant numberCountry
European Research Council (ERC)771965European Union
CitationJournal: 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
DepositionApr 23, 2023-
Header (metadata) releaseMay 1, 2024-
Map releaseMay 1, 2024-
UpdateMay 15, 2024-
Current statusMay 15, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_17192.png

Downloads & links

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Map

FileDownload / File: emd_17192.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotation2.62 Ang map of ASCT2-Syncytin-1.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 400 pix.
= 292.4 Å		0.73 Å/pix.
x 400 pix.
= 292.4 Å		0.73 Å/pix.
x 400 pix.
= 292.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.731 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0694
Minimum - Maximum-0.23648334 - 0.4735075
Average (Standard dev.)0.00012760822 (±0.012432237)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 292.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_17192_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_17192_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of ASCT2 with Synctin-1

EntireName: Complex of ASCT2 with Synctin-1
Components
  • Complex: Complex of ASCT2 with Synctin-1
    • Complex: Alanine Serine Cysteine Transporter 2
      • Protein or peptide: Neutral amino acid transporter B(0)
    • Complex: Syncytin-1
      • Protein or peptide: Syncytin-1
  • Ligand: ALANINE

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Supramolecule #1: Complex of ASCT2 with Synctin-1

SupramoleculeName: Complex of ASCT2 with Synctin-1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Molecular weightTheoretical: 180 kDa/nm

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Supramolecule #2: Alanine Serine Cysteine Transporter 2

SupramoleculeName: Alanine Serine Cysteine Transporter 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Syncytin-1

SupramoleculeName: Syncytin-1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Neutral amino acid transporter B(0)

MacromoleculeName: Neutral amino acid transporter B(0) / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 58.984566 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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)

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Macromolecule #2: Syncytin-1

MacromoleculeName: Syncytin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 49.24593 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: 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

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Macromolecule #3: ALANINE

MacromoleculeName: ALANINE / type: ligand / ID: 3 / Number of copies: 2 / Formula: ALA
Molecular weightTheoretical: 89.093 Da
Chemical component information

ChemComp-ALA:
ALANINE / Alanine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration9 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
100.0 mMNaClSodium chlorideSodium Chloride
5.0 mMC3H7NO2L-AlanineAlanine
25.0 mMC8H18N2O4SHepes
0.05 %C24H44O12Sucrose Monododecanoate
0.01 %C31H50O4.C4H11NO3Cholesteryl Hemisuccinate Tris Salt
GridModel: 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
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 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 opticsPhase plate: VOLTA PHASE PLATE / Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV
Sample stageCooling holder cryogen: NITROGEN
SoftwareName: EPU (ver. 2)
Image recordingFilm 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

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Image processing

Particle selectionNumber selected: 4018074
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6mpb

Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Details: Need to ask
Final reconstructionAlgorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 2.62 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3) / Number images used: 136195
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChainDetails

6mpb

source_name: PDB, initial_model_type: experimental model

a8f1

residue_range: 40-64, source_name: AlphaFold, initial_model_type: in silico modelThe alphafold model was used to model the N-terminal beta sheet of suppressyn.
SoftwareName: Coot (ver. 0.9.8.3)
RefinementSpace: REAL / Protocol: FLEXIBLE FIT / Overall B value: 60.1
Output model

PDB-8ouh:
Complex of human ASCT2 with Syncytin-1

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