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- EMDB-33538: Cryo-EM structure of human IgM-Fc in complex with the J chain and... -
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Open data
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Basic information
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Title | Cryo-EM structure of human IgM-Fc in complex with the J chain and the DBL domain of DBLMSP | |||||||||
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![]() | malaria / immunoglobin / IMMUNE SYSTEM | |||||||||
Function / homology | ![]() hexameric IgM immunoglobulin complex / IgM B cell receptor complex / dimeric IgA immunoglobulin complex / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / IgA binding / pre-B cell allelic exclusion / IgM immunoglobulin complex ...hexameric IgM immunoglobulin complex / IgM B cell receptor complex / dimeric IgA immunoglobulin complex / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / IgA binding / pre-B cell allelic exclusion / IgM immunoglobulin complex / glomerular filtration / CD22 mediated BCR regulation / immunoglobulin receptor binding / positive regulation of respiratory burst / humoral immune response / Scavenging of heme from plasma / antigen binding / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / antibacterial humoral response / protein-containing complex assembly / protein-macromolecule adaptor activity / defense response to Gram-negative bacterium / blood microparticle / adaptive immune response / Potential therapeutics for SARS / host cell surface receptor binding / immune response / innate immune response / cell surface / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.71 Å | |||||||||
![]() | Shen H / Ji C / Xiao J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M. Authors: Chenggong Ji / Hao Shen / Chen Su / Yaxin Li / Shihua Chen / Thomas H Sharp / Junyu Xiao / ![]() ![]() Abstract: Plasmodium falciparum causes the most severe malaria in humans. Immunoglobulin M (IgM) serves as the first line of humoral defense against infection and potently activates the complement pathway to ...Plasmodium falciparum causes the most severe malaria in humans. Immunoglobulin M (IgM) serves as the first line of humoral defense against infection and potently activates the complement pathway to facilitate P. falciparum clearance. A number of P. falciparum proteins bind IgM, leading to immune evasion and severe disease. However, the underlying molecular mechanisms remain unknown. Here, using high-resolution cryo-electron microscopy, we delineate how P. falciparum proteins VAR2CSA, TM284VAR1, DBLMSP, and DBLMSP2 target IgM. Each protein binds IgM in a different manner, and together they present a variety of Duffy-binding-like domain-IgM interaction modes. We further show that these proteins interfere directly with IgM-mediated complement activation in vitro, with VAR2CSA exhibiting the most potent inhibitory effect. These results underscore the importance of IgM for human adaptation of P. falciparum and provide critical insights into its immune evasion mechanism. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 118.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18 KB 18 KB | Display Display | ![]() |
Images | ![]() | 63.2 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 115.8 MB 115.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7y09MC ![]() 7y0hC ![]() 7y0jC ![]() 7yg2C 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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33538_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33538_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Ternary complex of human IgM-Fc with the J chain and the DBL doma...
Entire | Name: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP |
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Components |
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-Supramolecule #1: Ternary complex of human IgM-Fc with the J chain and the DBL doma...
Supramolecule | Name: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #2: Putative erythrocyte membrane protein
Supramolecule | Name: Putative erythrocyte membrane protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Immunoglobulin heavy constant mu
Supramolecule | Name: Immunoglobulin heavy constant mu / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: Immunoglobulin J chain
Supramolecule | Name: Immunoglobulin J chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: Putative erythrocyte membrane protein
Macromolecule | Name: Putative erythrocyte membrane protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 75.107406 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DSNLRNGLLN NSLDLTNGLN NKDNSFIDSK IEEHENKSYQ NKDNNISIVG QDVPITSVDS SKIINANDLE GNSIDDTKGL SVTNSGFDD GSAFGGGLPF SGYSPLQGNH NKCPDENFCK GIKNVLSCPP KNSTGRNGDW ISVAVKESST TNKGVLVPPR R KKLCLRNI ...String: DSNLRNGLLN NSLDLTNGLN NKDNSFIDSK IEEHENKSYQ NKDNNISIVG QDVPITSVDS SKIINANDLE GNSIDDTKGL SVTNSGFDD GSAFGGGLPF SGYSPLQGNH NKCPDENFCK GIKNVLSCPP KNSTGRNGDW ISVAVKESST TNKGVLVPPR R KKLCLRNI NQVWHRIKDE KNFKEEFVKV ALGESNALMK HYKEKNLNAL TAIKYGFSDM GDIIKGTDLI DYQITKNINR AL DKILGNE TSNDKIKKRV DWWEANKSAF WDAFMCGYKV HIGNKPCPEH DNMDRIPQYL RWFREWGTYV CSEYKNKFEN VIE LCNVRQ ITNQNDSQLL EISKEDKCKG ALKHYEEWVN RRRPEWKGQC DKFEKEKSKY EDTKSRTAEI YLKEICSECD CKYK DLDNT FKEFKDNVTL LKAVIDNKKN QDSLTTTSLS TSINSVRDSS NLDQRGNITT SQGNSHRATV VQQADQTNRL DNVNS VTQR GNNNYNNNLE RGLGSGALPG TNIITEEKYS LELIKLTSKD EEDIIKHNED VREEIEEQQE DIEEDEEELE NEGEET KEE DDEEKNETND TEDTDDTEDT EDIEEENEEK ELSNQQQSEK KSISKVDEDS YRILSVSYKD NNEVKNVAES IVKKLFS LF NDNNNLETIF KGLT UniProtKB: Putative erythrocyte membrane protein |
-Macromolecule #2: Immunoglobulin heavy constant mu
Macromolecule | Name: Immunoglobulin heavy constant mu / type: protein_or_peptide / ID: 2 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.875766 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ASAWSHPQFE KGGGSGGGSG GSAWSHPQFE KIDTTIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGFS PRQIQVSWLR EGKQVGSGV TTDQVQAEAK ESGPTTYKVT STLTIKESDW LGQSMFTCRV DHRGLTFQQN ASSMCVPDQD TAIRVFAIPP S FASIFLTK ...String: ASAWSHPQFE KGGGSGGGSG GSAWSHPQFE KIDTTIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGFS PRQIQVSWLR EGKQVGSGV TTDQVQAEAK ESGPTTYKVT STLTIKESDW LGQSMFTCRV DHRGLTFQQN ASSMCVPDQD TAIRVFAIPP S FASIFLTK STKLTCLVTD LTTYDSVTIS WTRQNGEAVK THTNISESHP NATFSAVGEA SICEDDWNSG ERFTCTVTHT DL PSPLKQT ISRPKGVALH RPDVYLLPPA REQLNLRESA TITCLVTGFS PADVFVQWMQ RGQPLSPEKY VTSAPMPEPQ APG RYFAHS ILTVSEEEWN TGETYTCVVA HEALPNRVTE RTVDKSTGKP TLYNVSLVMS DTAGTCY UniProtKB: Immunoglobulin heavy constant mu |
-Macromolecule #3: Immunoglobulin J chain
Macromolecule | Name: Immunoglobulin J chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.483329 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EDERIVLVDN KCKCARITSR IIRSSEDPNE DIVERNIRII VPLNNRENIS DPTSPLRTRF VYHLSDLCKK CDPTEVELDN QIVTATQSN ICDEDSATET CYTYDRNKCY TAVVPLVYGG ETKMVETALT PDACYPD UniProtKB: Immunoglobulin J chain |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 10 / 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
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.71 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 391618 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |