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- EMDB-40568: Structure of human SIgA1 in complex with Streptococcus pyogenes p... -

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Basic information

Entry
Database: EMDB / ID: EMD-40568
TitleStructure of human SIgA1 in complex with Streptococcus pyogenes protein M4 (Arp4)
Map data
Sample
  • Complex: Complex of human secretory Immunoglobulin A with group A streptococcus protein M4 (Arp4)
    • Complex: human secretory immunoglobulin A1
      • Protein or peptide: Immunoglobulin heavy constant alpha 1
      • Protein or peptide: Secretory component
      • Protein or peptide: Immunoglobulin J chain
    • Complex: M4 (Arp4) from Streptococcus pyogenes
      • Protein or peptide: IgA receptor
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsSecretory immunoglobulin A / SIgA / IgA / group A streptococcus / Streptococcus pyogenes M protein / M4 / Arp4 / infectious disease / protein complex / IMMUNE SYSTEM
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 / glomerular filtration / detection of chemical stimulus involved in sensory perception of bitter taste / IgA immunoglobulin complex / IgG immunoglobulin complex / azurophil granule membrane / receptor clustering / positive regulation of respiratory burst / humoral immune response / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / complement activation, classical pathway / Cell surface interactions at the vascular wall / antigen binding / B cell receptor signaling pathway / epidermal growth factor receptor signaling pathway / protein-macromolecule adaptor activity / antibacterial humoral response / protein-containing complex assembly / adaptive immune response / receptor complex / blood microparticle / immune response / innate immune response / Neutrophil degranulation / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
M protein repeat / M protein repeat / Immunoglobulin J chain / Immunoglobulin J chain / M protein-type anchor domain / YSIRK type signal peptide / YSIRK Gram-positive signal peptide / LPXTG cell wall anchor motif / Gram-positive cocci surface proteins LPxTG motif profile. / LPXTG cell wall anchor domain ...M protein repeat / M protein repeat / Immunoglobulin J chain / Immunoglobulin J chain / M protein-type anchor domain / YSIRK type signal peptide / YSIRK Gram-positive signal peptide / LPXTG cell wall anchor motif / Gram-positive cocci surface proteins LPxTG motif profile. / LPXTG cell wall anchor domain / Immunoglobulin / Immunoglobulin domain / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin subtype / Immunoglobulin / 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 / IgA receptor
Similarity search - Component
Biological speciesHomo sapiens (human) / Streptococcus pyogenes (bacteria) / Streptococcus pyogenes serotype M4 (bacteria)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsLiu Q / Stadtmueller BM
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI165570 United States
CitationJournal: Nat Commun / Year: 2023
Title: SIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions.
Authors: Qianqiao Liu / Beth M Stadtmueller /
Abstract: Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, mediate IgA effector functions; ...Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, mediate IgA effector functions; however, human pathogen Streptococcus pyogenes has evolved surface-protein virulence factors, including M4, that also engage the CD89-binding site on IgA. Despite human mucosa serving as a reservoir for pathogens, SIgA interactions with CD89 and M4 remain poorly understood. Here we report cryo-EM structures of M4-SIgA and CD89-SIgA complexes, which unexpectedly reveal different SIgA-binding stoichiometry for M4 and CD89. Structural data, supporting experiments, and modeling indicate that copies of SIgA bound to S. pyogenes M4 will adopt similar orientations on the bacterium surface and leave one host FcαR binding site open. Results suggest unappreciated functional consequences associated with SIgA binding to host and bacterial FcαRs relevant to understanding host-microbe co-evolution, IgA effector functions and improving the outcomes of group A Streptococcus infection.
History
DepositionApr 20, 2023-
Header (metadata) releaseOct 25, 2023-
Map releaseOct 25, 2023-
UpdateNov 8, 2023-
Current statusNov 8, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_40568.png

Downloads & links

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Map

FileDownload / File: emd_40568.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.95 Å
Density
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-4.12417 - 5.99065
Average (Standard dev.)-0.00012605234 (±0.082236744)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 342.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_40568_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_40568_half_map_1.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: #1

Fileemd_40568_half_map_2.map
Projections & Slices
AxesZYX

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Histogram (log scale)

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Sample components

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Entire : Complex of human secretory Immunoglobulin A with group A streptoc...

EntireName: Complex of human secretory Immunoglobulin A with group A streptococcus protein M4 (Arp4)
Components
  • Complex: Complex of human secretory Immunoglobulin A with group A streptococcus protein M4 (Arp4)
    • Complex: human secretory immunoglobulin A1
      • Protein or peptide: Immunoglobulin heavy constant alpha 1
      • Protein or peptide: Secretory component
      • Protein or peptide: Immunoglobulin J chain
    • Complex: M4 (Arp4) from Streptococcus pyogenes
      • Protein or peptide: IgA receptor
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Complex of human secretory Immunoglobulin A with group A streptoc...

SupramoleculeName: Complex of human secretory Immunoglobulin A with group A streptococcus protein M4 (Arp4)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4

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Supramolecule #2: human secretory immunoglobulin A1

SupramoleculeName: human secretory immunoglobulin A1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: M4 (Arp4) from Streptococcus pyogenes

SupramoleculeName: M4 (Arp4) from Streptococcus pyogenes / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 / Details: ectodomain of M4
Source (natural)Organism: Streptococcus pyogenes (bacteria) / Strain: M4

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Macromolecule #1: Immunoglobulin heavy constant alpha 1

MacromoleculeName: Immunoglobulin heavy constant alpha 1 / type: protein_or_peptide / ID: 1
Details: The sequence of the Fab region is not included due to legal reasons.
Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.687488 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT WSESGQGVTA RNFPPSQDAS GDLYTTSSQL TLPATQCLAG KSVTCHVKH YTNPSQDVTV PCPVPSTPPT PSPSTPPTPS PSCCHPRLSL HRPALEDLLL GSEANLTCTL TGLRDASGVT F TWTPSSGK ...String:
ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT WSESGQGVTA RNFPPSQDAS GDLYTTSSQL TLPATQCLAG KSVTCHVKH YTNPSQDVTV PCPVPSTPPT PSPSTPPTPS PSCCHPRLSL HRPALEDLLL GSEANLTCTL TGLRDASGVT F TWTPSSGK SAVQGPPERD LCGCYSVSSV LPGCAEPWNH GKTFTCTAAY PESKTPLTAT LSKSGNTFRP EVHLLPPPSE EL ALNELVT LTCLARGFSP KDVLVRWLQG SQELPREKYL TWASRQEPSQ GTTTFAVTSI LRVAAEDWKK GDTFSCMVGH EAL PLAFTQ KTIDRLAGKP THVNVSVVMA EVDGTCY

UniProtKB: Immunoglobulin heavy constant alpha 1

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Macromolecule #2: Secretory component

MacromoleculeName: Secretory component / type: protein_or_peptide / ID: 2 / Details: secretory component / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 61.095578 KDa
Recombinant expressionOrganism: Homo sapiens (human)
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 EERHHHHHH

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: Homo sapiens (human)
SequenceString:
QEDERIVLVD NKCKCARITS RIIRSSEDPN EDIVERNIRI IVPLNNRENI SDPTSPLRTR FVYHLSDLCK KCDPTEVELD NQIVTATQS NICDEDSATE TCYTYDRNKC YTAVVPLVYG GETKMVETAL TPDACYPD

UniProtKB: Immunoglobulin J chain

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Macromolecule #4: IgA receptor

MacromoleculeName: IgA receptor / type: protein_or_peptide / ID: 4 / Details: ectodomain of M4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Streptococcus pyogenes serotype M4 (bacteria) / Strain: M4
Molecular weightTheoretical: 37.352664 KDa
Recombinant expressionOrganism: Escherichia coli BL21 (bacteria)
SequenceString: AEIKKPQADS AWNWPKEYNA LLKENEELKV EREKYLSYAD DKEKDPQYRA LMGENQDLRK REGQYQDKIE ELEKERKEKQ ERQEQLERQ YQIEADKHYQ EQQKKHQQEQ QQLEAEKQKL AKDKQISDAS RQGLSRDLEA SRAAKKELEA EHQKLKEEKQ I SDASRQGL ...String:
AEIKKPQADS AWNWPKEYNA LLKENEELKV EREKYLSYAD DKEKDPQYRA LMGENQDLRK REGQYQDKIE ELEKERKEKQ ERQEQLERQ YQIEADKHYQ EQQKKHQQEQ QQLEAEKQKL AKDKQISDAS RQGLSRDLEA SRAAKKELEA EHQKLKEEKQ I SDASRQGL SRDLEASREA KKKVEADLAA LTAEHQKLKE DKQISDASRQ GLSRDLEASR EAKKKVEADL AEANSKLQAL EK LNKELEE GKKLSEKEKA ELQARLEAEA KALKEQLAKQ AEELAKLKGN QTPNAKVAPQ ANRSRSAMTQ QKRTLPSTHH HHH H

UniProtKB: IgA receptor

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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
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 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:

6ue7

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 200000
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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