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Yorodumi- EMDB-14119: Structure of the human MHC I peptide-loading complex editing module -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14119 | |||||||||
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Title | Structure of the human MHC I peptide-loading complex editing module | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / protein disulfide-isomerase / positive regulation of dendritic cell chemotaxis ...MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / protein disulfide-isomerase / positive regulation of dendritic cell chemotaxis / Assembly of Viral Components at the Budding Site / ATF6 (ATF6-alpha) activates chaperone genes / negative regulation of trophoblast cell migration / cortical granule / cellular response to electrical stimulus / nuclear receptor-mediated glucocorticoid signaling pathway / complement component C1q complex binding / regulation of meiotic nuclear division / negative regulation of retinoic acid receptor signaling pathway / response to glycoside / endoplasmic reticulum quality control compartment / sequestering of calcium ion / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / hormone binding / disulfide oxidoreductase activity / negative regulation of intracellular steroid hormone receptor signaling pathway / regulation of protein complex stability / nuclear export signal receptor activity / phospholipase C activity / cardiac muscle cell differentiation / molecular sequestering activity / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / positive regulation of extrinsic apoptotic signaling pathway / cellular response to interleukin-7 / Scavenging by Class A Receptors / protein maturation by protein folding / Scavenging by Class F Receptors / cortical actin cytoskeleton organization / positive regulation of memory T cell activation / T cell mediated cytotoxicity directed against tumor cell target / TAP complex binding / nuclear androgen receptor binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell proliferation / cellular response to lithium ion / CD8 receptor binding / protein disulfide isomerase activity / MHC class I protein binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / response to testosterone / endoplasmic reticulum exit site / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / protein-disulfide reductase activity / TAP binding / protein localization to nucleus / protection from natural killer cell mediated cytotoxicity / negative regulation of neuron differentiation / smooth endoplasmic reticulum / positive regulation of cell cycle / beta-2-microglobulin binding / phagocytic vesicle / T cell receptor binding / detection of bacterium / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / ERAD pathway / extrinsic apoptotic signaling pathway / endocytic vesicle lumen / protein folding chaperone / endoplasmic reticulum-Golgi intermediate compartment membrane / response to endoplasmic reticulum stress / protein export from nucleus / positive regulation of endothelial cell migration / acrosomal vesicle / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / negative regulation of receptor binding / DAP12 interactions / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / platelet aggregation / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / peptide binding / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / regulation of iron ion transport / response to molecule of bacterial origin Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / human (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.73 Å | |||||||||
Authors | Domnick A / Susac L / Trowitzsch S / Thomas C / Tampe R | |||||||||
Funding support | European Union, 2 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Molecular basis of MHC I quality control in the peptide loading complex. Authors: Alexander Domnick / Christian Winter / Lukas Sušac / Leon Hennecke / Mario Hensen / Nicole Zitzmann / Simon Trowitzsch / Christoph Thomas / Robert Tampé / Abstract: Major histocompatibility complex class I (MHC I) molecules are central to adaptive immunity. Their assembly, epitope selection, and antigen presentation are controlled by the MHC I glycan through a ...Major histocompatibility complex class I (MHC I) molecules are central to adaptive immunity. Their assembly, epitope selection, and antigen presentation are controlled by the MHC I glycan through a sophisticated network of chaperones and modifying enzymes. However, the mechanistic integration of the corresponding processes remains poorly understood. Here, we determine the multi-chaperone-client interaction network of the peptide loading complex (PLC) and report the PLC editing module structure by cryogenic electron microscopy at 3.7 Å resolution. Combined with epitope-proofreading studies of the PLC in near-native lipid environment, these data show that peptide-receptive MHC I molecules are stabilized by multivalent chaperone interactions including the calreticulin-engulfed mono-glucosylated MHC I glycan, which only becomes accessible for processing by α-glucosidase II upon loading of optimal epitopes. Our work reveals allosteric coupling between peptide-MHC I assembly and glycan processing. This inter-process communication defines the onset of an adaptive immune response and provides a prototypical example of the tightly coordinated events in endoplasmic reticulum quality control. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14119.map.gz | 166.7 MB | EMDB map data format | |
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Header (meta data) | emd-14119-v30.xml emd-14119.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
Images | emd_14119.png | 70.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14119 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14119 | HTTPS FTP |
-Validation report
Summary document | emd_14119_validation.pdf.gz | 358.6 KB | Display | EMDB validaton report |
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Full document | emd_14119_full_validation.pdf.gz | 358.1 KB | Display | |
Data in XML | emd_14119_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_14119_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14119 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14119 | HTTPS FTP |
-Related structure data
Related structure data | 7qpdMC 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_14119.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : editing module of peptide-loading complex
Entire | Name: editing module of peptide-loading complex |
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Components |
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-Supramolecule #1: editing module of peptide-loading complex
Supramolecule | Name: editing module of peptide-loading complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Beta-2-microglobulin
Macromolecule | Name: Beta-2-microglobulin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 11.74816 KDa |
Sequence | String: IQRTPKIQVY SRHPAENGKS NFLNCYVSGF HPSDIEVDLL KNGERIEKVE HSDLSFSKDW SFYLLYYTEF TPTEKDEYAC RVNHVTLSQ PKIVKWDRDM |
-Macromolecule #2: Tapasin
Macromolecule | Name: Tapasin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 45.761184 KDa |
Sequence | String: GPAVIECWFV EDASGKGLAK RPGALLLRQG PGEPPPRPDL DPELYLSVHD PAGALQAAFR RYPRGAPAPH CEMSRFVPLP ASAKWASGL TPAQNCPRAL DGAWLMVSIS SPVLSLSSLL RPQPEPQQEP VLITMATVVL TVLTHTPAPR VRLGQDALLD L SFAYMPPT ...String: GPAVIECWFV EDASGKGLAK RPGALLLRQG PGEPPPRPDL DPELYLSVHD PAGALQAAFR RYPRGAPAPH CEMSRFVPLP ASAKWASGL TPAQNCPRAL DGAWLMVSIS SPVLSLSSLL RPQPEPQQEP VLITMATVVL TVLTHTPAPR VRLGQDALLD L SFAYMPPT SEAASSLAPG PPPFGLEWRR QHLGKGHLLL AATPGLNGQM PAAQEGAVAF AAWDDDEPWG PWTGNGTFWL PR VQPFQEG TYLATIHLPY LQGQVTLELA VYKPPKVSLM PATLARAAPG EAPPELLCLV SHFYPSGGLE VEWELRGGPG GRS QKAEGQ RWLSALRHHS DGSVSLSGHL QPPPVTTEQH GARYACRIHH PSLPASGRSA EVTLEVAGLS GPSLEDSVGL FLSA FLLLG LFKALGWAAV YLSTCKDSKK KAE |
-Macromolecule #3: Protein disulfide-isomerase A3
Macromolecule | Name: Protein disulfide-isomerase A3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: protein disulfide-isomerase |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 54.341102 KDa |
Sequence | String: SDVLELTDDN FESRISDTGS AGLMLVEFFA PWCGHCKRLA PEYEAAATRL KGIVPLAKVD CTANTNTCNK YGVSGYPTLK IFRDGEEAG AYDGPRTADG IVSHLKKQAG PASVPLRTEE EFKKFISDKD ASIVGFFDDS FSEAHSEFLK AASNLRDNYR F AHTNVESL ...String: SDVLELTDDN FESRISDTGS AGLMLVEFFA PWCGHCKRLA PEYEAAATRL KGIVPLAKVD CTANTNTCNK YGVSGYPTLK IFRDGEEAG AYDGPRTADG IVSHLKKQAG PASVPLRTEE EFKKFISDKD ASIVGFFDDS FSEAHSEFLK AASNLRDNYR F AHTNVESL VNEYDDNGEG IILFRPSHLT NKFEDKTVAY TEQKMTSGKI KKFIQENIFG ICPHMTEDNK DLIQGKDLLI AY YDVDYEK NAKGSNYWRN RVMMVAKKFL DAGHKLNFAV ASRKTFSHEL SDFGLESTAG EIPVVAIRTA KGEKFVMQEE FSR DGKALE RFLQDYFDGN LKRYLKSEPI PESNDGPVKV VVAENFDEIV NNENKDVLIE FYAPWCGHCK NLEPKYKELG EKLS KDPNI VIAKMDATAN DVPSPYEVRG FPTIYFSPAN KKLNPKKYEG GRELSDFISY LQREATNPPV IQEEKPKKKK KAQED L |
-Macromolecule #4: HLA class I histocompatibility antigen, A-3 alpha chain
Macromolecule | Name: HLA class I histocompatibility antigen, A-3 alpha chain type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 38.363535 KDa |
Sequence | String: GSHSMRYFFT SVSRPGRGEP RFIAVGYVDD TQFVRFDSDA ASQRMEPRAP WIEQEGPEYW DQETRNVKAQ SQTDRVDLGT LRGYYNQSE AGSHTIQIMY GCDVGSDGRF LRGYRQDAYD GKDYIALNED LRSWTAADMA AQITKRKWEA AHEAEQLRAY L DGTCVEWL ...String: GSHSMRYFFT SVSRPGRGEP RFIAVGYVDD TQFVRFDSDA ASQRMEPRAP WIEQEGPEYW DQETRNVKAQ SQTDRVDLGT LRGYYNQSE AGSHTIQIMY GCDVGSDGRF LRGYRQDAYD GKDYIALNED LRSWTAADMA AQITKRKWEA AHEAEQLRAY L DGTCVEWL RRYLENGKET LQRTDPPKTH MTHHPISDHE ATLRCWALGF YPAEITLTWQ RDGEDQTQDT ELVETRPAGD GT FQKWAAV VVPSGEEQRY TCHVQHEGLP KPLTLRWELS SQPTIPIVGI IAGLVLLGAV ITGAVVAAVM WRRKSSDRKG GSY TQAASS DSAQGSDVSL TACKV |
-Macromolecule #5: Calreticulin
Macromolecule | Name: Calreticulin / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 46.523211 KDa |
Sequence | String: EPAVYFKEQF LDGDGWTSRW IESKHKSDFG KFVLSSGKFY GDEEKDKGLQ TSQDARFYAL SASFEPFSNK GQTLVVQFTV KHEQNIDCG GGYVKLFPNS LDQTDMHGDS EYNIMFGPDI CGPGTKKVHV IFNYKGKNVL INKDIRCKDD EFTHLYTLIV R PDNTYEVK ...String: EPAVYFKEQF LDGDGWTSRW IESKHKSDFG KFVLSSGKFY GDEEKDKGLQ TSQDARFYAL SASFEPFSNK GQTLVVQFTV KHEQNIDCG GGYVKLFPNS LDQTDMHGDS EYNIMFGPDI CGPGTKKVHV IFNYKGKNVL INKDIRCKDD EFTHLYTLIV R PDNTYEVK IDNSQVESGS LEDDWDFLPP KKIKDPDASK PEDWDERAKI DDPTDSKPED WDKPEHIPDP DAKKPEDWDE EM DGEWEPP VIQNPEYKGE WKPRQIDNPD YKGTWIHPEI DNPEYSPDPS IYAYDNFGVL GLDLWQVKSG TIFDNFLITN DEA YAEEFG NETWGVTKAA EKQMKDKQDE EQRLKEEEED KKRKEEEEAE DKEDDEDKDE DEEDEEDKEE DEEEDVPGQA KDEL |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 68.0 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: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Details: Patch CTF |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.73 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 97952 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |