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Yorodumi- EMDB-41021: Transporter associated with antigen processing (TAP) in the apo state -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41021 | |||||||||
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Title | Transporter associated with antigen processing (TAP) in the apo state | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ABC transporter / antigen processing / peptide transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / ABC-type peptide transporter activity / tapasin binding / ABC-type antigen peptide transporter / ABC-type peptide antigen transporter activity / TAP complex / TAP1 binding / oligopeptide export from mitochondrion / TAP2 binding / peptide antigen transport ...antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / ABC-type peptide transporter activity / tapasin binding / ABC-type antigen peptide transporter / ABC-type peptide antigen transporter activity / TAP complex / TAP1 binding / oligopeptide export from mitochondrion / TAP2 binding / peptide antigen transport / MHC class Ib protein binding / cytosol to endoplasmic reticulum transport / ABC-type oligopeptide transporter activity / peptide transport / peptide transmembrane transporter activity / MHC class I protein binding / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / centriolar satellite / endoplasmic reticulum-Golgi intermediate compartment membrane / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / response to molecule of bacterial origin / MHC class I peptide loading complex / T cell mediated cytotoxicity / antigen processing and presentation of endogenous peptide antigen via MHC class I / transmembrane transport / ADP binding / defense response / positive regulation of T cell mediated cytotoxicity / phagocytic vesicle membrane / peptide antigen binding / protein transport / ER-Phagosome pathway / adaptive immune response / mitochondrial inner membrane / nuclear speck / endoplasmic reticulum membrane / endoplasmic reticulum / protein homodimerization activity / ATP hydrolysis activity / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Lee J / Oldham ML / Chen J | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Principles of peptide selection by the transporter associated with antigen processing. Authors: James Lee / Michael L Oldham / Victor Manon / Jue Chen / Abstract: Our ability to fight pathogens relies on major histocompatibility complex class I (MHC-I) molecules presenting diverse antigens on the surface of diseased cells. The transporter associated with ...Our ability to fight pathogens relies on major histocompatibility complex class I (MHC-I) molecules presenting diverse antigens on the surface of diseased cells. The transporter associated with antigen processing (TAP) transports nearly the entire repertoire of antigenic peptides into the endoplasmic reticulum for MHC-I loading. How TAP transports peptides specific for MHC-I is unclear. In this study, we used cryo-EM to determine a series of structures of human TAP, both in the absence and presence of peptides with various sequences and lengths. The structures revealed that peptides of eight or nine residues in length bind in a similarly extended conformation, despite having little sequence overlap. We also identified two peptide-anchoring pockets on either side of the transmembrane cavity, each engaging one end of a peptide with primarily main chain atoms. Occupation of both pockets results in a global conformational change in TAP, bringing the two halves of the transporter closer together to prime it for isomerization and ATP hydrolysis. Shorter peptides are able to bind to each pocket separately but are not long enough to bridge the cavity to bind to both simultaneously. Mutations that disrupt hydrogen bonds with the N and C termini of peptides almost abolish MHC-I surface expression. Our findings reveal that TAP functions as a molecular caliper that selects peptides according to length rather than sequence, providing antigen diversity for MHC-I presentation. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41021.map.gz | 230.1 MB | EMDB map data format | |
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Header (meta data) | emd-41021-v30.xml emd-41021.xml | 19.6 KB 19.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41021_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_41021.png | 61.1 KB | ||
Filedesc metadata | emd-41021.cif.gz | 6.6 KB | ||
Others | emd_41021_additional_1.map.gz emd_41021_half_map_1.map.gz emd_41021_half_map_2.map.gz | 122.2 MB 226.8 MB 226.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41021 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41021 | HTTPS FTP |
-Validation report
Summary document | emd_41021_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_41021_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_41021_validation.xml.gz | 21.8 KB | Display | |
Data in CIF | emd_41021_validation.cif.gz | 27.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41021 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41021 | HTTPS FTP |
-Related structure data
Related structure data | 8t46MC 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_41021.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.839 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_41021_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_41021_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41021_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Transporter associated with antigen processing
Entire | Name: Transporter associated with antigen processing |
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Components |
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-Supramolecule #1: Transporter associated with antigen processing
Supramolecule | Name: Transporter associated with antigen processing / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: Complex of TAP1 and TAP2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 156 KDa |
-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: Homo sapiens (human) |
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: Homo sapiens (human) |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 6 mg/mL | |||||||||||||||
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Buffer | pH: 6.5 Component:
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Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. / Pretreatment - Atmosphere: AIR | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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: 2.5 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |