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- EMDB-43501: Cryo-EM structure of human invariant chain in complex with HLA-DQ -
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Open data
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Basic information
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Title | Cryo-EM structure of human invariant chain in complex with HLA-DQ | |||||||||
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![]() | Antigen presentation / membrane protein / trimeric complex / IMMUNE SYSTEM | |||||||||
Function / homology | ![]() 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 / T cell activation involved in immune response / positive regulation of type 2 immune response / T cell selection / positive regulation of prostaglandin biosynthetic process / negative thymic T cell selection / negative regulation of viral entry into host cell / MHC class II receptor activity / MHC class II protein binding / negative regulation of mature B cell apoptotic process / positive thymic T cell selection / positive regulation of monocyte differentiation / CD4 receptor binding / positive regulation of kinase activity / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of neutrophil chemotaxis / vacuole / positive regulation of macrophage cytokine production / prostaglandin biosynthetic process / positive regulation of T cell differentiation / cytokine receptor activity / regulation of macrophage activation / transport vesicle membrane / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / nitric-oxide synthase binding / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / response to type II interferon / cytokine binding / antigen processing and presentation / negative regulation of DNA damage response, signal transduction by p53 class mediator / humoral immune response / chaperone cofactor-dependent protein refolding / Generation of second messenger molecules / PD-1 signaling / immunoglobulin mediated immune response / positive regulation of chemokine production / positive regulation of B cell proliferation / protein folding chaperone / MHC class II antigen presentation / multivesicular body / negative regulation of cell migration / lysosomal lumen / trans-Golgi network membrane / positive regulation of interleukin-8 production / lumenal side of endoplasmic reticulum membrane / Cell surface interactions at the vascular wall / intracellular protein transport / clathrin-coated endocytic vesicle membrane / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class II protein complex / MHC class II protein complex / peptide antigen binding / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of interleukin-6 production / endocytic vesicle membrane / positive regulation of peptidyl-tyrosine phosphorylation / Interferon gamma signaling / positive regulation of immune response / positive regulation of fibroblast proliferation / Downstream TCR signaling / late endosome / positive regulation of T cell activation / MHC class II protein complex binding / late endosome membrane / amyloid-beta binding / T cell receptor signaling pathway / protein-containing complex assembly / positive regulation of canonical NF-kappaB signal transduction / adaptive immune response / positive regulation of MAPK cascade / positive regulation of viral entry into host cell / positive regulation of ERK1 and ERK2 cascade / lysosome / protein stabilization / positive regulation of protein phosphorylation / immune response / Golgi membrane / lysosomal membrane / external side of plasma membrane / positive regulation of gene expression / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / cell surface / protein-containing complex / extracellular exosome / identical protein binding / membrane / nucleus Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.12 Å | |||||||||
![]() | Wang N / Caveney NA / Jude KM / Garcia KC | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 45.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.3 KB 17.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.9 KB | Display | ![]() |
Images | ![]() | 148.2 KB | ||
Masks | ![]() | 52.7 MB | ![]() | |
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 48.9 MB 48.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 670.9 KB | Display | ![]() |
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Full document | ![]() | 670.5 KB | Display | |
Data in XML | ![]() | 15.3 KB | Display | |
Data in CIF | ![]() | 19.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8vspMC ![]() 8vrwC 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: 1.2585 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: #2
File | emd_43501_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Trimeric complex of invariant chain associated with HLA-DQ alpha ...
Entire | Name: Trimeric complex of invariant chain associated with HLA-DQ alpha and beta |
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Components |
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-Supramolecule #1: Trimeric complex of invariant chain associated with HLA-DQ alpha ...
Supramolecule | Name: Trimeric complex of invariant chain associated with HLA-DQ alpha and beta type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 330 KDa |
-Macromolecule #1: HLA class II histocompatibility antigen, DQ alpha 1 chain
Macromolecule | Name: HLA class II histocompatibility antigen, DQ alpha 1 chain type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 31.599943 KDa |
Recombinant expression | Organism: Mammalia (mammals) |
Sequence | String: MILNKALMLG ALALTTVMSP CGGEDIVADH VASYGVNLYQ SYGPSGQYTH EFDGDEQFYV DLGRKETVWC LPVLRQFRFD PQFALTNIA VLKHNLNSLI KRSNSTAATN EVPEVTVFSK SPVTLGQPNI LICLVDNIFP PVVNITWLSN GHSVTEGVSE T SFLSKSDH ...String: MILNKALMLG ALALTTVMSP CGGEDIVADH VASYGVNLYQ SYGPSGQYTH EFDGDEQFYV DLGRKETVWC LPVLRQFRFD PQFALTNIA VLKHNLNSLI KRSNSTAATN EVPEVTVFSK SPVTLGQPNI LICLVDNIFP PVVNITWLSN GHSVTEGVSE T SFLSKSDH SFFKISYLTL LPSAEESYDC KVEHWGLDKP LLKHWEPEIP APMSELTETV VCALGLSVGL VGIVVGTVFI IR GLRSVGA SRHQGPLAAA LEVLFQGPGA AEDQVDPRLI DGKHHHHHHH H UniProtKB: HLA class II histocompatibility antigen, DQ alpha 1 chain |
-Macromolecule #2: HLA class II histocompatibility antigen, DQ beta 1 chain
Macromolecule | Name: HLA class II histocompatibility antigen, DQ beta 1 chain type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 33.798309 KDa |
Recombinant expression | Organism: Mammalia (mammals) |
Sequence | String: MSWKKALRIP GGLRAATVTL MLAMLSTPVA EGRDSPEDFV YQFKAMCYFT NGTERVRYVT RYIYNREEYA RFDSDVEVYR AVTPLGPPD AEYWNSQKEV LERTRAELDT VCRHNYQLEL RTTLQRRVEP TVTISPSRTE ALNHHNLLVC SVTDFYPAQI K VRWFRNDQ ...String: MSWKKALRIP GGLRAATVTL MLAMLSTPVA EGRDSPEDFV YQFKAMCYFT NGTERVRYVT RYIYNREEYA RFDSDVEVYR AVTPLGPPD AEYWNSQKEV LERTRAELDT VCRHNYQLEL RTTLQRRVEP TVTISPSRTE ALNHHNLLVC SVTDFYPAQI K VRWFRNDQ EETTGVVSTP LIRNGDWTFQ ILVMLEMTPQ HGDVYTCHVE HPSLQNPITV EWRAQSESAQ SKMLSGIGGF VL GLIFLGL GLIIHHRSQK GLLHAAALEV LFQGPGAAED QVDPRLIDGK HHHHHHHH UniProtKB: HLA class II histocompatibility antigen, DQ beta 1 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: ![]() |
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 |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 3 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
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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: ![]() |
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 |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-8vsp: |