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- EMDB-33805: Cryo-EM structure of human IgM-Fc in complex with the J chain and... -

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Basic information

Entry
Database: EMDB / ID: EMD-33805
TitleCryo-EM structure of human IgM-Fc in complex with the J chain and the DBL domain of DBLMSP2
Map data
Sample
  • Complex: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP2
    • Complex: Putative erythrocyte membrane protein
      • Protein or peptide: DBLMSP2
    • Complex: Immunoglobulin heavy constant mu
      • Protein or peptide: Immunoglobulin heavy constant mu
    • Complex: Immunoglobulin J chain
      • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsmalaria / immunoglobin / IMMUNE SYSTEM
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 / 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 / Potential therapeutics for SARS / adaptive immune response / 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
Immunoglobulin J chain / Immunoglobulin J chain / Duffy-antigen binding / Duffy-antigen binding superfamily / Duffy binding domain / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set ...Immunoglobulin J chain / Immunoglobulin J chain / Duffy-antigen binding / Duffy-antigen binding superfamily / Duffy binding domain / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
DBLMSP2 / Immunoglobulin J chain / Immunoglobulin heavy constant mu
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.32 Å
AuthorsShen H / Ji C / Xiao J
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: 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
DepositionJul 9, 2022-
Header (metadata) releaseMar 29, 2023-
Map releaseMar 29, 2023-
UpdateOct 9, 2024-
Current statusOct 9, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_33805.png

Downloads & links

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Map

FileDownload / File: emd_33805.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 320 pix.
= 342.4 Å		1.07 Å/pix.
x 320 pix.
= 342.4 Å		1.07 Å/pix.
x 320 pix.
= 342.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.17
Minimum - Maximum-0.94987833 - 1.5757134
Average (Standard dev.)-0.0003278388 (±0.027558627)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 342.40002 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_33805_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_33805_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Ternary complex of human IgM-Fc with the J chain and the DBL doma...

EntireName: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP2
Components
  • Complex: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP2
    • Complex: Putative erythrocyte membrane protein
      • Protein or peptide: DBLMSP2
    • Complex: Immunoglobulin heavy constant mu
      • Protein or peptide: Immunoglobulin heavy constant mu
    • Complex: Immunoglobulin J chain
      • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Ternary complex of human IgM-Fc with the J chain and the DBL doma...

SupramoleculeName: Ternary complex of human IgM-Fc with the J chain and the DBL domain of DBLMSP2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)

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Supramolecule #2: Putative erythrocyte membrane protein

SupramoleculeName: Putative erythrocyte membrane protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Immunoglobulin heavy constant mu

SupramoleculeName: Immunoglobulin heavy constant mu / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: Immunoglobulin J chain

SupramoleculeName: Immunoglobulin J chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3

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Macromolecule #1: DBLMSP2

MacromoleculeName: DBLMSP2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Molecular weightTheoretical: 36.305992 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: TINLGFNKCP TEEICKDFSN LPQCRKNVHE RNNWLGSSVK NFSSDNKGVL VPPRRQSLCL RITLQDFRTK KKKEGDFEKF IYSYASSEA RKLRTIHNNN LEKAHQAIRY SFADIGNIIR GDDMMDTPTS KETITYLEKV LKIYNENNDK PKDAKKWWTE N RHHVWEAM ...String:
TINLGFNKCP TEEICKDFSN LPQCRKNVHE RNNWLGSSVK NFSSDNKGVL VPPRRQSLCL RITLQDFRTK KKKEGDFEKF IYSYASSEA RKLRTIHNNN LEKAHQAIRY SFADIGNIIR GDDMMDTPTS KETITYLEKV LKIYNENNDK PKDAKKWWTE N RHHVWEAM MCGYQSAQKD NQCTGYGNID DIPQFLRWFR EWGTYVCEES EKNMNTLKAV CFPKQPRTEA NPALTVHENE MC SSTLKKY EEWYNKRKTE WTEQSIKYNN DKINYTDIKT LSPSEYLIEK CPECKCTKKN LQDVFELTFD

UniProtKB: DBLMSP2

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Macromolecule #2: Immunoglobulin heavy constant mu

MacromoleculeName: Immunoglobulin heavy constant mu / type: protein_or_peptide / ID: 2 / Number of copies: 10 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 41.875766 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

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Macromolecule #3: Immunoglobulin J chain

MacromoleculeName: Immunoglobulin J chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15.483329 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EDERIVLVDN KCKCARITSR IIRSSEDPNE DIVERNIRII VPLNNRENIS DPTSPLRTRF VYHLSDLCKK CDPTEVELDN QIVTATQSN ICDEDSATET CYTYDRNKCY TAVVPLVYGG ETKMVETALT PDACYPD

UniProtKB: Immunoglobulin J chain

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 10 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6kxs

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 458396
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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