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Yorodumi- EMDB-43488: Cryo-EM structure of human invariant chain in complex with HLA-DR15 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-43488 | |||||||||
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Title | Cryo-EM structure of human invariant chain in complex with HLA-DR15 | |||||||||
Map data | Sharpen map after cryoSPRARC DeepEhancer | |||||||||
Sample |
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Keywords | Antigen presentation / membrane protein / trimeric complex / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information negative regulation of peptide secretion / macrophage migration inhibitory factor signaling pathway / NOS2-CD74 complex / MHC class II protein binding, via antigen binding groove / antigen processing and presentation of endogenous antigen / positive regulation of dendritic cell antigen processing and presentation / negative regulation of T cell differentiation / macrophage migration inhibitory factor binding / positive regulation of macrophage migration inhibitory factor signaling pathway / protein trimerization ...negative regulation of peptide secretion / macrophage migration inhibitory factor signaling pathway / NOS2-CD74 complex / MHC class II protein binding, via antigen binding groove / antigen processing and presentation of endogenous antigen / positive regulation of dendritic cell antigen processing and presentation / negative regulation of T cell differentiation / macrophage migration inhibitory factor binding / positive regulation of macrophage migration inhibitory factor signaling pathway / protein trimerization / macrophage migration inhibitory factor receptor complex / positive regulation of cytokine-mediated signaling pathway / regulation of interleukin-4 production / regulation of interleukin-10 production / myeloid dendritic cell antigen processing and presentation / antigen processing and presentation of endogenous peptide antigen via MHC class II / T cell activation involved in immune response / autolysosome membrane / positive regulation of type 2 immune response / positive regulation of prostaglandin biosynthetic process / regulation of T-helper cell differentiation / T cell selection / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / negative thymic T cell selection / negative regulation of viral entry into host cell / MHC class II receptor activity / positive regulation of T cell mediated immune response to tumor cell / MHC class II protein binding / positive regulation of CD4-positive, alpha-beta T cell activation / antigen processing and presentation of peptide or polysaccharide antigen via MHC class II / negative regulation of mature B cell apoptotic process / positive regulation of memory T cell differentiation / positive thymic T cell selection / positive regulation of kinase activity / CD4 receptor binding / positive regulation of monocyte differentiation / inflammatory response to antigenic stimulus / vacuole / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of neutrophil chemotaxis / cytokine receptor activity / prostaglandin biosynthetic process / positive regulation of macrophage cytokine production / positive regulation of T cell differentiation / intermediate filament / regulation of macrophage activation / polysaccharide binding / T-helper 1 type immune response / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / transport vesicle membrane / nitric-oxide synthase binding / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / response to type II interferon / positive regulation of insulin secretion involved in cellular response to glucose stimulus / antigen processing and presentation / cytokine binding / negative regulation of DNA damage response, signal transduction by p53 class mediator / chaperone cofactor-dependent protein refolding / macrophage differentiation / negative regulation of type II interferon production / humoral immune response / Generation of second messenger molecules / immunological synapse / PD-1 signaling / epidermis development / immunoglobulin mediated immune response / T cell receptor binding / negative regulation of T cell proliferation / detection of bacterium / positive regulation of chemokine production / positive regulation of B cell proliferation / protein folding chaperone / MHC class II antigen presentation / multivesicular body / lysosomal lumen / trans-Golgi network membrane / negative regulation of cell migration / positive regulation of interleukin-8 production / Cell surface interactions at the vascular wall / lumenal side of endoplasmic reticulum membrane / negative regulation of inflammatory response to antigenic stimulus / protein tetramerization / intracellular protein transport / clathrin-coated endocytic vesicle membrane / ER to Golgi transport vesicle membrane / structural constituent of cytoskeleton / cognition / peptide antigen assembly with MHC class II protein complex / MHC class II protein complex / positive regulation of interleukin-6 production / positive regulation of T cell mediated cytotoxicity / peptide antigen binding / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of immune response / Interferon gamma signaling / positive regulation of fibroblast proliferation / endocytic vesicle membrane / positive regulation of T cell activation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.03 Å | |||||||||
Authors | Wang N / Caveney NA / Jude KM / Garcia KC | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Structural insights into human MHC-II association with invariant chain. Authors: Nan Wang / Deepa Waghray / Nathanael A Caveney / Kevin M Jude / K Christopher Garcia / Abstract: The loading of processed peptides on to major histocompatibility complex II (MHC-II) molecules for recognition by T cells is vital to cell-mediated adaptive immunity. As part of this process, MHC-II ...The loading of processed peptides on to major histocompatibility complex II (MHC-II) molecules for recognition by T cells is vital to cell-mediated adaptive immunity. As part of this process, MHC-II associates with the invariant chain (Ii) during biosynthesis in the endoplasmic reticulum to prevent premature peptide loading and to serve as a scaffold for subsequent proteolytic processing into MHC-II-CLIP. Cryo-electron microscopy structures of full-length Human Leukocyte Antigen-DR (HLA-DR) and HLA-DQ complexes associated with Ii, resolved at 3.0 to 3.1 Å, elucidate the trimeric assembly of the HLA/Ii complex and define atomic-level interactions between HLA, Ii transmembrane domains, loop domains, and class II-associated invariant chain peptides (CLIP). Together with previous structures of MHC-II peptide loading intermediates DO and DM, our findings complete the structural path governing class II antigen presentation. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_43488.map.gz | 288.3 MB | EMDB map data format | |
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Header (meta data) | emd-43488-v30.xml emd-43488.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_43488_fsc.xml | 14.8 KB | Display | FSC data file |
Images | emd_43488.png | 159.7 KB | ||
Masks | emd_43488_msk_1.map | 343 MB | Mask map | |
Filedesc metadata | emd-43488.cif.gz | 6.1 KB | ||
Others | emd_43488_half_map_1.map.gz emd_43488_half_map_2.map.gz | 318.7 MB 318.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43488 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43488 | HTTPS FTP |
-Validation report
Summary document | emd_43488_validation.pdf.gz | 698.1 KB | Display | EMDB validaton report |
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Full document | emd_43488_full_validation.pdf.gz | 697.7 KB | Display | |
Data in XML | emd_43488_validation.xml.gz | 23.9 KB | Display | |
Data in CIF | emd_43488_validation.cif.gz | 31.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43488 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43488 | HTTPS FTP |
-Related structure data
Related structure data | 8vrwMC 8vspC 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_43488.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpen map after cryoSPRARC DeepEhancer | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.653 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_43488_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_43488_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_43488_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Trimeric complex of invariant chain associated with HLA-DRA1 and ...
Entire | Name: Trimeric complex of invariant chain associated with HLA-DRA1 and HLA-DRB1 |
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Components |
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-Supramolecule #1: Trimeric complex of invariant chain associated with HLA-DRA1 and ...
Supramolecule | Name: Trimeric complex of invariant chain associated with HLA-DRA1 and HLA-DRB1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 330 KDa |
-Macromolecule #1: HLA class II histocompatibility antigen, DR alpha chain
Macromolecule | Name: HLA class II histocompatibility antigen, DR alpha chain type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 32.418971 KDa |
Recombinant expression | Organism: Mammalia (mammals) |
Sequence | String: MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD MAKKETVWRL EEFGRFASFE AQGALANIA VDKANLEIMT KRSNYTPITN VPPEVTVLTN SPVELREPNV LICFIDKFTP PVVNVTWLRN GKPVTTGVSE T VFLPREDH ...String: MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD MAKKETVWRL EEFGRFASFE AQGALANIA VDKANLEIMT KRSNYTPITN VPPEVTVLTN SPVELREPNV LICFIDKFTP PVVNVTWLRN GKPVTTGVSE T VFLPREDH LFRKFHYLPF LPSTEDVYDC RVEHWGLDEP LLKHWEFDAP SPLPETTENV VCALGLTVGL VGIIIGTIFI IK GLRKSNA AERRGPLAAA LEVLFQGPGA AEDQVDPRLI DGKHHHHHHH H UniProtKB: HLA class II histocompatibility antigen, DR alpha chain |
-Macromolecule #2: HLA class II histocompatibility antigen, DRB1 beta chain
Macromolecule | Name: HLA class II histocompatibility antigen, DRB1 beta chain type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 33.768199 KDa |
Recombinant expression | Organism: Mammalia (mammals) |
Sequence | String: MVCLKLPGGS CMTALTVTLM VLSSPLALSG DTRPRFLWQP KRECHFFNGT ERVRFLDRYF YNQEESVRFD SDVGEFRAVT ELGRPDAEY WNSQKDILEQ ARAAVDTYCR HNYGVVESFT VQRRVQPKVT VYPSKTQPLQ HHNLLVCSVS GFYPGSIEVR W FLNGQEEK ...String: MVCLKLPGGS CMTALTVTLM VLSSPLALSG DTRPRFLWQP KRECHFFNGT ERVRFLDRYF YNQEESVRFD SDVGEFRAVT ELGRPDAEY WNSQKDILEQ ARAAVDTYCR HNYGVVESFT VQRRVQPKVT VYPSKTQPLQ HHNLLVCSVS GFYPGSIEVR W FLNGQEEK AGMVSTGLIQ NGDWTFQTLV MLETVPRSGE VYTCQVEHPS VTSPLTVEWR ARSESAQSKM LSGVGGFVLG LL FLGAGLF IYFRNQKGHS GLQPTGFLSA AALEVLFQGP GAAEDQVDPR LIDGKHHHHH HHH UniProtKB: HLA class II histocompatibility antigen, DRB1 beta chain |
-Macromolecule #3: HLA class II histocompatibility antigen gamma chain
Macromolecule | Name: HLA class II histocompatibility antigen gamma chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 34.901906 KDa |
Recombinant expression | Organism: Mammalia (mammals) |
Sequence | String: MDYKDDDDAG TSRHRRRSRS CREDQKPVMD DQRDLISNNE QLPMLGRRPG APESKCSRGA LYTGFSILVT LLLAGQATTA YFLYQQQGR LDKLTVTSQN LQLENLRMKL PKPPKPVSKM RMATPLLMQA LPMGALPQGP MQNATKYGNM TEDHVMHLLQ N ADPLKVYP ...String: MDYKDDDDAG TSRHRRRSRS CREDQKPVMD DQRDLISNNE QLPMLGRRPG APESKCSRGA LYTGFSILVT LLLAGQATTA YFLYQQQGR LDKLTVTSQN LQLENLRMKL PKPPKPVSKM RMATPLLMQA LPMGALPQGP MQNATKYGNM TEDHVMHLLQ N ADPLKVYP PLKGSFPENL RHLKNTMETI DWKVFESWMH HWLLFEMSRH SLEQKPTDAP PKVLTKCQEE VSHIPAVHPG SF RPKCDEN GNYLPLQCYG SIGYCWCVFP NGTEVPNTRS RGHHNCSESL ELEDPSSGLG VTKQDLGPVP M UniProtKB: HLA class II histocompatibility antigen gamma chain |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 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: 60.0 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: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | PDB-8vrw: |