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Yorodumi- EMDB-8482: Cryo-EM structure of the human TAP ATP-Binding Cassette Transporter -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8482 | |||||||||
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Title | Cryo-EM structure of the human TAP ATP-Binding Cassette Transporter | |||||||||
Map data | Human TAP ATP-Binding Cassette Transporter, full map from Frealign alignment, scaled to molecule, B-factor corrected to -150 Angstrom^2, and moved into new padded unit cell | |||||||||
Sample |
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Keywords | membrane / protein / ABC transporter / antigen / presentation / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane / antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / tapasin binding / ABC-type antigen peptide transporter / ABC-type peptide antigen transporter activity / TAP complex / ABC-type peptide transporter activity / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent / symbiont-mediated suppression of host adaptive immune response / peptide antigen transport ...vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane / antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / tapasin binding / ABC-type antigen peptide transporter / ABC-type peptide antigen transporter activity / TAP complex / ABC-type peptide transporter activity / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent / symbiont-mediated suppression of host adaptive immune response / peptide antigen transport / MHC class Ib protein binding / : / symbiont-mediated suppression of host antigen processing and presentation / cytosol to endoplasmic reticulum transport / Translocases; Catalysing the translocation of amino acids and peptides; Linked to the hydrolysis of a nucleoside triphosphate / peptide transport / peptide transmembrane transporter activity / TAP1 binding / TAP2 binding / antigen processing and presentation of peptide antigen via MHC class I / centriolar satellite / ATPase-coupled transmembrane transporter activity / MHC class I protein binding / viral process / endoplasmic reticulum-Golgi intermediate compartment membrane / ADP binding / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / defense response / transmembrane transport / MHC class I peptide loading complex / antigen processing and presentation of endogenous peptide antigen via MHC class I / phagocytic vesicle membrane / peptide antigen binding / protein transport / ER-Phagosome pathway / host cell cytoplasm / adaptive immune response / membrane => GO:0016020 / nuclear speck / host cell nucleus / endoplasmic reticulum membrane / endoplasmic reticulum / ATP hydrolysis activity / protein homodimerization activity / ATP binding / membrane / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Human herpesvirus 1 (Herpes simplex virus type 1) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.97 Å | |||||||||
Authors | Oldham ML / Chen J | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2016 Title: Structure of the transporter associated with antigen processing trapped by herpes simplex virus. Authors: Michael L Oldham / Nikolaus Grigorieff / Jue Chen / Abstract: The transporter associated with antigen processing (TAP) is an ATP-binding cassette (ABC) transporter essential to cellular immunity against viral infection. Some persistent viruses have evolved ...The transporter associated with antigen processing (TAP) is an ATP-binding cassette (ABC) transporter essential to cellular immunity against viral infection. Some persistent viruses have evolved strategies to inhibit TAP so that they may go undetected by the immune system. The herpes simplex virus for example evades immune surveillance by blocking peptide transport with a small viral protein ICP47. In this study, we determined the structure of human TAP bound to ICP47 by electron cryo-microscopy (cryo-EM) to 4.0 Å. The structure shows that ICP47 traps TAP in an inactive conformation distinct from the normal transport cycle. The specificity and potency of ICP47 inhibition result from contacts between the tip of the helical hairpin and the apex of the transmembrane cavity. This work provides a clear molecular description of immune evasion by a persistent virus. It also establishes the molecular structure of TAP to facilitate mechanistic studies of the antigen presentation process. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8482.map.gz | 59.4 MB | EMDB map data format | |
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Header (meta data) | emd-8482-v30.xml emd-8482.xml | 29.1 KB 29.1 KB | Display Display | EMDB header |
Images | emd_8482.png | 173 KB | ||
Filedesc metadata | emd-8482.cif.gz | 7.1 KB | ||
Others | emd_8482_additional_1.map.gz emd_8482_additional_2.map.gz emd_8482_additional_3.map.gz emd_8482_additional_4.map.gz emd_8482_additional_5.map.gz emd_8482_additional_6.map.gz | 59.4 MB 59.4 MB 59.5 MB 8.3 MB 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8482 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8482 | HTTPS FTP |
-Related structure data
Related structure data | 5u1dMC 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 |
EM raw data | EMPIAR-10816 (Title: Cryo-electron microscopy reconstruction of human TAP Transporter bound to Herpes Simplex Virus 1 Inhibitor ICP47 Data size: 1.5 TB Data #1: Unaligned and uncorrected multiframe movies of human TAP Transporter bound to Herpes Simplex Virus 1 Inhibitor ICP47 [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_8482.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, full map from Frealign alignment, scaled to molecule, B-factor corrected to -150 Angstrom^2, and moved into new padded unit cell | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.36133 Å / Y: 0.45312 Å / Z: 0.45312 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Human TAP ATP-Binding Cassette Transporter, half map 2...
File | emd_8482_additional_1.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, half map 2 from Frealign alignment before move to new unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human TAP ATP-Binding Cassette Transporter, half map 1...
File | emd_8482_additional_2.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, half map 1 from Frealign alignment before move to new unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human TAP ATP-Binding Cassette Transporter, full map 1...
File | emd_8482_additional_3.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, full map 1 from Frealign alignment, scaled to molecule, and moved into new padded unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human TAP ATP-Binding Cassette Transporter, full map from...
File | emd_8482_additional_4.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, full map from Frealign alignment before moving to new unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human TAP ATP-Binding Cassette Transporter, half map 2...
File | emd_8482_additional_5.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, half map 2 from Frealign alignment, scaled to molecule, and moved into new padded unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human TAP ATP-Binding Cassette Transporter, half map 1...
File | emd_8482_additional_6.map | ||||||||||||
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Annotation | Human TAP ATP-Binding Cassette Transporter, half map 1 from Frealign alignment, scaled to molecule, and moved into new padded unit cell | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TAP ATP-Binding Cassette Transporter
Entire | Name: TAP ATP-Binding Cassette Transporter |
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Components |
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-Supramolecule #1: TAP ATP-Binding Cassette Transporter
Supramolecule | Name: TAP ATP-Binding Cassette Transporter / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Antigen peptide transporter 1
Macromolecule | Name: Antigen peptide transporter 1 / 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: 81.034289 KDa |
Recombinant expression | Organism: Komagataella pastoris (fungus) |
Sequence | String: MASSRCPAPR GCRCLPGASL AWLGTVLLLL ADWVLLRTAL PRIFSLLVPT ALPLLRVWAV GLSRWAVLWL GACGVLRATV GSKSENAGA QGWLAALKPL AAALGLALPG LALFRELISW GAPGSADSTR LLHWGSHPTA FVVSYAAALP AAALWHKLGS L WVPGGQGG ...String: MASSRCPAPR GCRCLPGASL AWLGTVLLLL ADWVLLRTAL PRIFSLLVPT ALPLLRVWAV GLSRWAVLWL GACGVLRATV GSKSENAGA QGWLAALKPL AAALGLALPG LALFRELISW GAPGSADSTR LLHWGSHPTA FVVSYAAALP AAALWHKLGS L WVPGGQGG SGNPVRRLLG CLGSETRRLS LFLVLVVLSS LGEMAIPFFT GRLTDWILQD GSADTFTRNL TLMSILTIAS AV LEFVGDG IYNNTMGHVH SHLQGEVFGA VLRQETEFFQ QNQTGNIMSR VTEDTSTLSD SLSENLSLFL WYLVRGLCLL GIM LWGSVS LTMVTLITLP LLFLLPKKVG KWYQLLEVQV RESLAKSSQV AIEALSAMPT VRSFANEEGE AQKFREKLQE IKTL NQKEA VAYAVNSWTT SISGMLLKVG ILYIGGQLVT SGAVSSGNLV TFVLYQMQFT QAVEVLLSIY PRVQKAVGSS EKIFE YLDR TPRCPPSGLL TPLHLEGLVQ FQDVSFAYPN RPDVLVLQGL TFTLRPGEVT ALVGPNGSGK STVAALLQNL YQPTGG QLL LDGKPLPQYE HRYLHRQVAA VGQEPQVFGR SLQENIAYGL TQKPTMEEIT AAAVKSGAHS FISGLPQGYD TEVDEAG SQ LSGGQRQAVA LARALIRKPC VLILDDATSA LDANSQLQVE QLLYESPERY SRSVLLITQH LSLVEQADHI LFLEGGAI R EGGTHQQLME KKGCYWAMVQ APADAPE UniProtKB: Antigen peptide transporter 1 |
-Macromolecule #2: Antigen peptide transporter 2
Macromolecule | Name: Antigen peptide transporter 2 / 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: 75.736508 KDa |
Recombinant expression | Organism: Komagataella pastoris (fungus) |
Sequence | String: MRLPDLRPWT SLLLVDAALL WLLQGPLGTL LPQGLPGLWL EGTLRLGGLW GLLKLRGLLG FVGTLLLPLC LATPLTVSLR ALVAGASRA PPARVASAPW SWLLVGYGAA GLSWSLWAVL SPPGAQEKEQ DQVNNKVLMW RLLKLSRPDL PLLVAAFFFL V LAVLGETL ...String: MRLPDLRPWT SLLLVDAALL WLLQGPLGTL LPQGLPGLWL EGTLRLGGLW GLLKLRGLLG FVGTLLLPLC LATPLTVSLR ALVAGASRA PPARVASAPW SWLLVGYGAA GLSWSLWAVL SPPGAQEKEQ DQVNNKVLMW RLLKLSRPDL PLLVAAFFFL V LAVLGETL IPHYSGRVID ILGGDFDPHA FASAIFFMCL FSFGSSLSAG CRGGCFTYTM SRINLRIREQ LFSSLLRQDL GF FQETKTG ELNSRLSSDT TLMSNWLPLN ANVLLRSLVK VVGLYGFMLS ISPRLTLLSL LHMPFTIAAE KVYNTRHQEV LRE IQDAVA RAGQVVREAV GGLQTVRSFG AEEHEVCRYK EALEQCRQLY WRRDLERALY LLVRRVLHLG VQMLMLSCGL QQMQ DGELT QGSLLSFMIY QESVGSYVQT LVYIYGDMLS NVGAAEKVFS YMDRQPNLPS PGTLAPTTLQ GVVKFQDVSF AYPNR PDRP VLKGLTFTLR PGEVTALVGP NGSGKSTVAA LLQNLYQPTG GQVLLDEKPI SQYEHCYLHS QVVSVGQEPV LFSGSV RNN IAYGLQSCED DKVMAAAQAA HADDFIQEME HGIYTDVGEK GSQLAAGQKQ RLAIARALVR DPRVLILDEA TSALDVQ CE QALQDWNSRG DRTVLVIAHR LQTVQRAHQI LVLQEGKLQK LAQL UniProtKB: Antigen peptide transporter 2 |
-Macromolecule #3: TAP transporter inhibitor ICP47
Macromolecule | Name: TAP transporter inhibitor ICP47 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human herpesvirus 1 (Herpes simplex virus type 1) |
Molecular weight | Theoretical: 9.850086 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: MSWALEMADT FLDNMRVGPR TYADVRDEIN KRGREDREAA RTAVHDPERP LLRSPGLLPE IAPNASLGVV HRRTGGTVTD SPRNPVTR UniProtKB: ICP47 protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: C-flat-1.2/1.3 4C / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 10 sec. / Pretreatment - Atmosphere: AIR | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 22 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 | Calibrated defocus max: 3.0 µm / Calibrated defocus min: 1.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 0.01 mm |
Specialist optics | Energy filter - Name: GIF |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Temperature | Min: 100.0 K / Max: 100.0 K |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 3875 / Average exposure time: 0.2 sec. / Average electron dose: 1.48 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 501973 |
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Startup model | Type of model: EMDB MAP EMDB ID: |
Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Number classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.97 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: FREALIGN (ver. 9.09) / Number images used: 501973 |
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: OTHER / Overall B value: 150 / Target criteria: R factor and FSC |
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Output model | PDB-5u1d: |