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- EMDB-17189: Structure of the human neutral amino acid transporter ASCT2 in co... -
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Open data
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Basic information
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Title | Structure of the human neutral amino acid transporter ASCT2 in complex with nanobody 469 | |||||||||
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![]() | Neutral aminoacid transmembrane transporter activity / ASCT2 / ![]() ![]() ![]() | |||||||||
Function / homology | ![]() glutamine secretion / L-glutamine import across plasma membrane / glutamine transport / L-glutamine transmembrane transporter activity / L-serine transmembrane transporter activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Canul-Tec J / Reyes N | |||||||||
Funding support | European Union, 1 items
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![]() | ![]() 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 | ![]() | 79 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.7 KB 22.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 57.7 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() | 77.7 MB 77.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8oudMC ![]() 8ouhC ![]() 8ouiC ![]() 8oujC 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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Voxel size | X=Y=Z: 0.934 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_17189_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17189_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Complex of human ASCT2 with Nanobody 69
Entire | Name: Complex of human ASCT2 with Nanobody 69 |
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Components |
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-Supramolecule #1: Complex of human ASCT2 with Nanobody 69
Supramolecule | Name: Complex of human ASCT2 with Nanobody 69 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Molecular weight | Theoretical: 200 KDa |
-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: ![]() ![]() |
-Supramolecule #3: Nanobody 69
Supramolecule | Name: Nanobody 69 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 56.638902 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MVADPPRDSK GLAAAEPTAN GGLALASIED QGAAAGGYCG SRDQVRRCLR ANLLVLLTVV AVVAGVALGL GVSGAGGALA LGPERLSAF VFPGELLLRL LRMIILPLVV CSLIGGAASL DPGALGRLGA WALLFFLVTT LLASALGVGL ALALQPGAAS A AINASVGA ...String: MVADPPRDSK GLAAAEPTAN GGLALASIED QGAAAGGYCG SRDQVRRCLR ANLLVLLTVV AVVAGVALGL GVSGAGGALA LGPERLSAF VFPGELLLRL LRMIILPLVV CSLIGGAASL DPGALGRLGA WALLFFLVTT LLASALGVGL ALALQPGAAS A AINASVGA AGSAENAPSK EVLDSFLDLA RNIFPSNLVS AAFRSYSTTY EERNITGTRV KVPVGQEVEG MNILGLVVFA IV FGVALRK LGPEGELLIR FFNSFNEATM VLVSWIMWYA PVGIMFLVAG KIVEMEDVGL LFARLGKYIL CCLLGHAIHG LLV LPLIYF LFTRKNPYRF LWGIVTPLAT AFGTSSSSAT LPLMMKCVEE NNGVAKHISR FILPIGATVN MDGAALFQCV AAVF IAQLS QQSLDFVKII TILVTATASS VGAAGIPAGG VLTLAIILEA VNLPVDHISL ILAVDWLVDR SCTVLNVEGD ALGAG LLQN YVDRTESRST EPELIQVKSE LPLDPLPVPT EEGNPLLKHY RGPAGDATVA SEKESVM UniProtKB: Neutral amino acid transporter B(0) |
-Macromolecule #2: Nanobody 469
Macromolecule | Name: Nanobody 469 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 13.792409 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: QVQLVESGGG LVQPGGSLRL SCAASGSIFR LDAMGWYRQA PGKQRELVAV IRSGGSTDYG DSVKGRFTIS RDNAKNTVYL QMNSLKPED TAVYYCNAVQ ILKTIYWGQG TQVTVSSHHH HHHEPEA |
-Macromolecule #3: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 3 / Number of copies: 9 |
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Molecular weight | Theoretical: 22.99 Da |
-Macromolecule #4: ALANINE
Macromolecule | Name: ALANINE / type: ligand / ID: 4 / Number of copies: 3 / Formula: ALA |
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Molecular weight | Theoretical: 89.093 Da |
Chemical component information | ![]() ChemComp-ALA: |
-Macromolecule #5: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 5 / Number of copies: 3 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #6: water
Macromolecule | Name: water / type: ligand / ID: 6 / Number of copies: 93 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 8.1 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.4 Component:
Details: 25 mM Hepes pH7.4, 100 mM NaCl, 5 mM L-Alanine, 0.05% DDS, 0.01% CHS. | ||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 10 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.03 kPa | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
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 |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 4344 / Average exposure time: 4.0 sec. / Average electron dose: 52.24 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Residue range: 43-489 / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 77.4 |
Output model | ![]() PDB-8oud: |