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- EMDB-20749: Structure of dimeric sIgA complex -

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Basic information

Entry
Database: EMDB / ID: EMD-20749
TitleStructure of dimeric sIgA complex
Map dataMain map of sIgA Dimer.
Sample
  • Complex: dimeric sIgA complex
    • Protein or peptide: Immunoglobulin heavy constant alpha 1
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


polymeric immunoglobulin receptor activity / immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor / dimeric IgA immunoglobulin complex / polymeric immunoglobulin binding / 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 / dimeric IgA immunoglobulin complex / polymeric immunoglobulin binding / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / Fc receptor signaling pathway / IgA binding / detection of chemical stimulus involved in sensory perception of bitter taste / glomerular filtration / IgA immunoglobulin complex / azurophil granule membrane / receptor clustering / immunoglobulin complex, circulating / IgG immunoglobulin complex / immunoglobulin receptor binding / 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 / protein-macromolecule adaptor activity / antibacterial humoral response / 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 / Immunoglobulin/major histocompatibility complex, conserved site ...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 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsKumar N / Arthur CP / Ciferri C / Matsumoto ML
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) releaseOct 16, 2019-
Map releaseFeb 19, 2020-
UpdateDec 2, 2020-
Current statusDec 2, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 3.2
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 3.2
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6ue7
  • Surface level: 3.2
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_20749.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMain map of sIgA Dimer.
Voxel sizeX=Y=Z: 1.0188 Å
Density
Contour LevelBy AUTHOR: 3.2 / Movie #1: 3.2
Minimum - Maximum-7.666398 - 19.458878
Average (Standard dev.)-0.014166938 (±0.36141795)
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-7.66619.459-0.014

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Supplemental data

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Additional map: -150 sharpened map of sIgA Dimer complex.

Fileemd_20749_additional.map
Annotation-150 sharpened map of sIgA Dimer complex.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : dimeric sIgA complex

EntireName: dimeric sIgA complex
Components
  • Complex: dimeric sIgA complex
    • Protein or peptide: Immunoglobulin heavy constant alpha 1
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: dimeric sIgA complex

SupramoleculeName: dimeric sIgA complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
Molecular weightTheoretical: 188 KDa

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Macromolecule #1: Immunoglobulin heavy constant alpha 1

MacromoleculeName: Immunoglobulin heavy constant alpha 1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.667172 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DYKDDDDKLV PRGSCHPRLS LHRPALEDLL LGSEANLTCT LTGLRDASGV TFTWTPSSGK SAVQGPPERD LCGCYSVSSV LPGCAEPWN HGKTFTCTAA YPESKTPLTA TLSKSGNTFR PEVHLLPPPS EELALNELVT LTCLARGFSP KDVLVRWLQG S QELPREKY ...String:
DYKDDDDKLV PRGSCHPRLS LHRPALEDLL LGSEANLTCT LTGLRDASGV TFTWTPSSGK SAVQGPPERD LCGCYSVSSV LPGCAEPWN HGKTFTCTAA YPESKTPLTA TLSKSGNTFR PEVHLLPPPS EELALNELVT LTCLARGFSP KDVLVRWLQG S QELPREKY LTWASRQEPS QGTTTFAVTS ILRVAAEDWK KGDTFSCMVG HEALPLAFTQ KTIDRLAGKP THVNVSVVMA EV DGTCY

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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

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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

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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 / N-Acetylglucosamine

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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

Concentration0.18 mg/mL
BufferpH: 7.2
GridModel: UltrAuFoil / Material: GOLD / Mesh: 400 / Pretreatment - Type: PLASMA CLEANING / Details: 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
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 165000
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 10.0 sec. / Average electron dose: 51.91 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: OTHER / Software - Name: cisTEM
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 233402

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