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- EMDB-20751: Structure of tetrameric sIgA complex (Class 2) -

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Basic information

Entry
Database: EMDB / ID: EMD-20751
TitleStructure of tetrameric sIgA complex (Class 2)
Map datatetrameric sIgA complex (Class 2)
Sample
  • Complex: tetrameric sIgA complex (Class 2)
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin J chain
    • Protein or peptide: Immunoglobulin heavy constant alpha 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsimmunoglobulin / IMMUNE SYSTEM
Function / homology
Function and homology information


polymeric immunoglobulin receptor activity / immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor / polymeric immunoglobulin binding / dimeric IgA immunoglobulin complex / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / Fc receptor signaling pathway / IgA binding ...polymeric immunoglobulin receptor activity / immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor / polymeric immunoglobulin binding / dimeric IgA immunoglobulin complex / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / Fc receptor signaling pathway / IgA binding / IgA immunoglobulin complex / detection of chemical stimulus involved in sensory perception of bitter taste / glomerular filtration / azurophil granule membrane / immunoglobulin receptor binding / immunoglobulin complex, circulating / receptor clustering / positive regulation of respiratory burst / humoral immune response / Scavenging of heme from plasma / complement activation, classical pathway / antigen binding / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / epidermal growth factor receptor signaling pathway / antibacterial humoral response / protein-macromolecule adaptor activity / protein-containing complex assembly / blood microparticle / adaptive immune response / receptor complex / immune response / innate immune response / Neutrophil degranulation / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Immunoglobulin J chain / Immunoglobulin J chain / : / Immunoglobulin / Immunoglobulin domain / : / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype ...Immunoglobulin J chain / Immunoglobulin J chain / : / Immunoglobulin / Immunoglobulin domain / : / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / 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
Immunoglobulin J chain / Polymeric immunoglobulin receptor / Immunoglobulin heavy constant alpha 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsKumar N / Arthur CP
CitationJournal: Science / Year: 2020
Title: Structure of the secretory immunoglobulin A core.
Authors: Nikit Kumar / Christopher P Arthur / Claudio Ciferri / Marissa L Matsumoto /
Abstract: Secretory immunoglobulin A (sIgA) represents the immune system's first line of defense against mucosal pathogens. IgAs are transported across the epithelium, as dimers and higher-order polymers, by ...Secretory immunoglobulin A (sIgA) represents the immune system's first line of defense against mucosal pathogens. IgAs are transported across the epithelium, as dimers and higher-order polymers, by the polymeric immunoglobulin receptor (pIgR). Upon reaching the luminal side, sIgAs mediate host protection and pathogen neutralization. In recent years, an increasing amount of attention has been given to IgA as a novel therapeutic antibody. However, despite extensive studies, sIgA structures have remained elusive. Here, we determine the atomic resolution structures of dimeric, tetrameric, and pentameric IgA-Fc linked by the joining chain (JC) and in complex with the secretory component of the pIgR. We suggest a mechanism in which the JC templates IgA oligomerization and imparts asymmetry for pIgR binding and transcytosis. This framework will inform the design of future IgA-based therapeutics.
History
DepositionSep 20, 2019-
Header (metadata) releaseFeb 19, 2020-
Map releaseFeb 19, 2020-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 2.5
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 2.5
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6ue9
  • Surface level: 2.5
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_20751.png

Downloads & links

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Map

FileDownload / File: emd_20751.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationtetrameric sIgA complex (Class 2)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.02 Å/pix.
x 384 pix.
= 391.219 Å		1.02 Å/pix.
x 384 pix.
= 391.219 Å		1.02 Å/pix.
x 384 pix.
= 391.219 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0188 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 2.5 / Movie #1: 2.5
Minimum - Maximum-8.025726000000001 - 18.104064999999999
Average (Standard dev.)-0.012513195 (±0.4200236)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 391.2192 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.01879947916671.01879947916671.0187994791667
M x/y/z384384384
origin x/y/z0.0000.0000.000
length x/y/z391.219391.219391.219
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ256256256
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS384384384
D min/max/mean-8.02618.104-0.013

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Supplemental data

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Additional map: -150 sharpened map of tetrameric sIgA (Class 2).

Fileemd_20751_additional.map
Annotation-150 sharpened map of tetrameric sIgA (Class 2).
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : tetrameric sIgA complex (Class 2)

EntireName: tetrameric sIgA complex (Class 2)
Components
  • Complex: tetrameric sIgA complex (Class 2)
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin J chain
    • Protein or peptide: Immunoglobulin heavy constant alpha 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: tetrameric sIgA complex (Class 2)

SupramoleculeName: tetrameric sIgA complex (Class 2) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2-#3, #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 294 KDa

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Macromolecule #1: Immunoglobulin heavy constant alpha 2

MacromoleculeName: Immunoglobulin heavy constant alpha 2 / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.682146 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DYKDDDDKLV PRGSCHPRLS LHRPALEDLL LGSEANLTCT LTGLRDASGA TFTWTPSSGK SAVQGPPERD LCGCYSVSSV LPGCAQPWN HGETFTCTAA HPELKTPLTA NITKSGNTFR PEVHLLPPPS EELALNELVT LTCLARGFSP KDVLVRWLQG S QELPREKY ...String:
DYKDDDDKLV PRGSCHPRLS LHRPALEDLL LGSEANLTCT LTGLRDASGA TFTWTPSSGK SAVQGPPERD LCGCYSVSSV LPGCAQPWN HGETFTCTAA HPELKTPLTA NITKSGNTFR PEVHLLPPPS EELALNELVT LTCLARGFSP KDVLVRWLQG S QELPREKY LTWASRQEPS QGTTTYAVTS ILRVAAEDWK KGETFSCMVG HEALPLAFTQ KTIDRLAGKP THINVSVVMA EA DGTCY

UniProtKB: Immunoglobulin heavy constant alpha 2

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Macromolecule #2: Polymeric immunoglobulin receptor

MacromoleculeName: Polymeric immunoglobulin receptor / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 65.154094 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: KSPIFGPEEV NSVEGNSVSI TCYYPPTSVN RHTRKYWCRQ GARGGCITLI SSEGYVSSKY AGRANLTNFP ENGTFVVNIA QLSQDDSGR YKCGLGINSR GLSFDVSLEV SQGPGLLNDT KVYTVDLGRT VTINCPFKTE NAQKRKSLYK QIGLYPVLVI D SSGYVNPN ...String:
KSPIFGPEEV NSVEGNSVSI TCYYPPTSVN RHTRKYWCRQ GARGGCITLI SSEGYVSSKY AGRANLTNFP ENGTFVVNIA QLSQDDSGR YKCGLGINSR GLSFDVSLEV SQGPGLLNDT KVYTVDLGRT VTINCPFKTE NAQKRKSLYK QIGLYPVLVI D SSGYVNPN YTGRIRLDIQ GTGQLLFSVV INQLRLSDAG QYLCQAGDDS NSNKKNADLQ VLKPEPELVY EDLRGSVTFH CA LGPEVAN VAKFLCRQSS GENCDVVVNT LGKRAPAFEG RILLNPQDKD GSFSVVITGL RKEDAGRYLC GAHSDGQLQE GSP IQAWQL FVNEESTIPR SPTVVKGVAG GSVAVLCPYN RKESKSIKYW CLWEGAQNGR CPLLVDSEGW VKAQYEGRLS LLEE PGNGT FTVILNQLTS RDAGFYWCLT NGDTLWRTTV EIKIIEGEPN LKVPGNVTAV LGETLKVPCH FPCKFSSYEK YWCKW NNTG CQALPSQDEG PSKAFVNCDE NSRLVSLTLN LVTRADEGWY WCGVKQGHFY GETAAVYVAV EERKAAGSRD VSLAKA DAA PDEKVLDSGF REIENKAIQD PRHHHHHH

UniProtKB: Polymeric immunoglobulin receptor

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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: 15.611458 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
QEDERIVLVD NKCKCARITS RIIRSSEDPN EDIVERNIRI IVPLNNRENI SDPTSPLRTR FVYHLSDLCK KCDPTEVELD NQIVTATQS NICDEDSATE TCYTYDRNKC YTAVVPLVYG GETKMVETAL TPDACYPD

UniProtKB: Immunoglobulin J chain

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 7 / 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: 7.2
GridDetails: unspecified
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average exposure time: 10.0 sec. / Average electron dose: 51.91 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 144523
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: OTHER / Software - Name: cisTEM

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