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- PDB-8skv: Structure of human SIgA1 in complex with Streptococcus pyogenes p... -

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Basic information

Entry
Database: PDB / ID: 8skv
TitleStructure of human SIgA1 in complex with Streptococcus pyogenes protein M4 (Arp4)
Components
  • (Immunoglobulin ...) x 2
  • IgA receptor
  • Secretory component
KeywordsIMMUNE SYSTEM / Secretory immunoglobulin A / SIgA / IgA / group A streptococcus / Streptococcus pyogenes M protein / M4 / Arp4 / infectious disease / protein complex
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 / IgG immunoglobulin complex / azurophil granule membrane / positive regulation of respiratory burst / receptor clustering / 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 / Immunoglobulin subtype / Immunoglobulin / 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 / IgA receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
Streptococcus pyogenes serotype M4 (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsLiu, Q. / Stadtmueller, B.M.
Funding support United States, 1items
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, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 25, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 8, 2023Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Immunoglobulin heavy constant alpha 1
B: Immunoglobulin heavy constant alpha 1
C: Immunoglobulin heavy constant alpha 1
D: Immunoglobulin heavy constant alpha 1
E: Secretory component
J: Immunoglobulin J chain
a: IgA receptor
b: IgA receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)305,40819
Polymers302,1628
Non-polymers3,24611
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Immunoglobulin ... , 2 types, 5 molecules ABCDJ

#1: Protein
Immunoglobulin heavy constant alpha 1 / Ig alpha-1 chain C region / Ig alpha-1 chain C region BUR / Ig alpha-1 chain C region TRO


Mass: 37687.488 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Details: The sequence of the Fab region is not included due to legal reasons.
Source: (gene. exp.) Homo sapiens (human) / Gene: IGHA1 / Cell line (production host): HEK Expi293F / Production host: Homo sapiens (human) / References: UniProt: P01876
#3: Protein Immunoglobulin J chain / Joining chain of multimeric IgA and IgM


Mass: 15611.458 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): HEK Expi293F / Production host: Homo sapiens (human) / References: UniProt: P01591

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Protein , 2 types, 3 molecules Eab

#2: Protein Secretory component / Polymeric immunoglobulin receptor


Mass: 61095.578 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: secretory component / Source: (gene. exp.) Homo sapiens (human) / Gene: PIGR / Cell line (production host): HEK Expi293F / Production host: Homo sapiens (human) / References: UniProt: P01833
#4: Protein IgA receptor


Mass: 37352.664 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: ectodomain of M4
Source: (gene. exp.) Streptococcus pyogenes serotype M4 (bacteria)
Strain: M4 / Gene: arp4 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P13050

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Sugars , 2 types, 11 molecules

#5: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#6: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 7
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Details

Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSourceDetails
1Complex of human secretory Immunoglobulin A with group A streptococcus protein M4 (Arp4)COMPLEX#1-#40MULTIPLE SOURCES
2human secretory immunoglobulin A1COMPLEX#1-#31RECOMBINANT
3M4 (Arp4) from Streptococcus pyogenesCOMPLEX#41RECOMBINANTectodomain of M4
Molecular weight
IDEntity assembly-IDExperimental value
11NO
21NO
31NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-IDStrain
22Homo sapiens (human)9606
33Streptococcus pyogenes (bacteria)404331M4
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDStrainCell
22Homo sapiens (human)9606HEK Expi293F
33Escherichia coli (E. coli)562BL21
Buffer solutionpH: 7
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 200000 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00212493
ELECTRON MICROSCOPYf_angle_d0.52217108
ELECTRON MICROSCOPYf_dihedral_angle_d4.6351820
ELECTRON MICROSCOPYf_chiral_restr0.0412055
ELECTRON MICROSCOPYf_plane_restr0.0042197

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