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- EMDB-0782: 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-0782
TitleCryo-EM structure of human IgM-Fc in complex with the J chain and the ectodomain of pIgR
Map dataThe primary map.
Sample
  • Complex: Ternary complex of IgM-Fc with the J chain and pIgR/SC
    • Protein or peptide: Polymeric immunoglobulin receptor
  • Protein or peptide: Immunoglobulin heavy constant mu
  • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


hexameric IgM immunoglobulin complex / polymeric immunoglobulin receptor activity / immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor / dimeric IgA immunoglobulin complex / IgM B cell receptor complex / polymeric immunoglobulin binding / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex ...hexameric IgM immunoglobulin complex / polymeric immunoglobulin receptor activity / immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor / dimeric IgA immunoglobulin complex / IgM B cell receptor 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 / IgM immunoglobulin complex / pre-B cell allelic exclusion / CD22 mediated BCR regulation / azurophil granule membrane / positive regulation of respiratory burst / receptor clustering / humoral immune response / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / 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 / defense response to Gram-negative bacterium / adaptive immune response / Potential therapeutics for SARS / receptor complex / blood microparticle / immune response / innate immune response / Neutrophil degranulation / cell surface / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Immunoglobulin J chain / Immunoglobulin J chain / 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 J chain / Immunoglobulin J chain / 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 mu
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsLi Y / Wang G / Xiao J
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: Science / Year: 2020
Title: Structural insights into immunoglobulin M.
Authors: Yaxin Li / Guopeng Wang / Ningning Li / Yuxin Wang / Qinyu Zhu / Huarui Chu / Wenjun Wu / Ying Tan / Feng Yu / Xiao-Dong Su / Ning Gao / Junyu Xiao /
Abstract: Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), ...Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.
History
DepositionSep 12, 2019-
Header (metadata) releaseJan 22, 2020-
Map releaseFeb 5, 2020-
UpdateDec 15, 2021-
Current statusDec 15, 2021Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.011
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.011
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6kxs
  • Surface level: 0.011
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_0782.png

Downloads & links

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Map

FileDownload / File: emd_0782.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThe primary map.
Voxel sizeX=Y=Z: 0.828 Å
Density
Contour LevelBy AUTHOR: 0.01 / Movie #1: 0.011
Minimum - Maximum-0.09893445 - 0.1187983
Average (Standard dev.)0.00022054034 (±0.0025811617)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 264.96 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.8280.8280.828
M x/y/z320320320
origin x/y/z0.0000.0000.000
length x/y/z264.960264.960264.960
α/β/γ90.00090.00090.000
start NX/NY/NZ-31-35-52
NX/NY/NZ11798209
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS320320320
D min/max/mean-0.0990.1190.000

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Supplemental data

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Mask #1

Fileemd_0782_msk_1.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 IgM-Fc with the J chain and pIgR/SC

EntireName: Ternary complex of IgM-Fc with the J chain and pIgR/SC
Components
  • Complex: Ternary complex of IgM-Fc with the J chain and pIgR/SC
    • Protein or peptide: Polymeric immunoglobulin receptor
  • Protein or peptide: Immunoglobulin heavy constant mu
  • Protein or peptide: Immunoglobulin J chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Ternary complex of IgM-Fc with the J chain and pIgR/SC

SupramoleculeName: Ternary complex of IgM-Fc with the J chain and pIgR/SC
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #1: Immunoglobulin heavy constant mu

MacromoleculeName: Immunoglobulin heavy constant mu / type: protein_or_peptide / ID: 1 / Details: N-ACETYL-D-GLUCOSAMINE / 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

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Macromolecule #2: Immunoglobulin J chain

MacromoleculeName: Immunoglobulin J chain / type: protein_or_peptide / ID: 2 / 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

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Macromolecule #3: Polymeric immunoglobulin receptor

MacromoleculeName: Polymeric immunoglobulin receptor / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 61.371875 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 EERHHHHHHH H

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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

Concentration0.4 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 59.74 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1183008
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
FSC plot (resolution estimation)

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