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Yorodumi- PDB-7yg2: Cryo-EM structure of human IgM-Fc in complex with the J chain and... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7yg2 | ||||||
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Title | Cryo-EM structure of human IgM-Fc in complex with the J chain and the DBL domain of DBLMSP2 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / malaria / immunoglobin | ||||||
Function / homology | Function and homology information 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 / immunoglobulin complex, circulating / positive regulation of respiratory burst / humoral immune response / Scavenging of heme from plasma / complement activation, classical pathway / 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-macromolecule adaptor activity / protein-containing complex assembly / 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 | Plasmodium falciparum (malaria parasite P. falciparum) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.32 Å | ||||||
Authors | Shen, H. / Ji, C. / Xiao, J. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2023 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yg2.cif.gz | 496.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yg2.ent.gz | 397.8 KB | Display | PDB format |
PDBx/mmJSON format | 7yg2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7yg2_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 7yg2_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 7yg2_validation.xml.gz | 80.2 KB | Display | |
Data in CIF | 7yg2_validation.cif.gz | 116.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yg/7yg2 ftp://data.pdbj.org/pub/pdb/validation_reports/yg/7yg2 | HTTPS FTP |
-Related structure data
Related structure data | 33805MC 7y09C 7y0hC 7y0jC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 36305.992 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum) Gene: DBLMSP2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: A0A0A7MCY3 | ||||||||||
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#2: Protein | Mass: 41875.766 Da / Num. of mol.: 10 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IGHM / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P01871 #3: Protein | | Mass: 15483.329 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JCHAIN, IGCJ, IGJ / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P01591 #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | Y | Has protein modification | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 458396 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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