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- EMDB-22591: Structure of Secretory IgM Core -

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Basic information

Entry
Database: EMDB / ID: EMD-22591
TitleStructure of Secretory IgM Core
Map dataSecretory IgM Core
Sample
  • Complex: Structure of the Human Secretory Immunoglobulin M Core
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin heavy constant mu
    • Protein or peptide: Immunoglobulin J chain
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 / pre-B cell allelic exclusion / IgM immunoglobulin complex / CD22 mediated BCR regulation / azurophil granule membrane / receptor clustering / immunoglobulin complex, circulating / immunoglobulin receptor binding / positive regulation of respiratory burst / humoral immune response / Scavenging of heme from plasma / complement activation, classical pathway / antigen binding / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / 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 / defense response to Gram-negative bacterium / Potential therapeutics for SARS / adaptive immune response / receptor complex / 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 subtype / Immunoglobulin / Immunoglobulin/major histocompatibility complex, conserved site / 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 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 mu
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsKumar N / Arthur CP / Ciferri C / Matsumoto ML
CitationJournal: Structure / Year: 2021
Title: Structure of the human secretory immunoglobulin M core.
Authors: Nikit Kumar / Christopher P Arthur / Claudio Ciferri / Marissa L Matsumoto /
Abstract: Immunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) ...Immunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through a highly conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.
History
DepositionSep 4, 2020-
Header (metadata) releaseJan 20, 2021-
Map releaseJan 20, 2021-
UpdateJun 16, 2021-
Current statusJun 16, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 5.5
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 5.5
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7k0c
  • Surface level: 5.5
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22591.png

Downloads & links

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Map

FileDownload / File: emd_22591.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSecretory IgM Core
Voxel sizeX=Y=Z: 1.2 Å
Density
Contour LevelBy AUTHOR: 4.5 / Movie #1: 5.5
Minimum - Maximum-24.536037 - 42.554035
Average (Standard dev.)-6.2426475e-13 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 480.00003 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.21.21.2
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z480.000480.000480.000
α/β/γ90.00090.00090.000
start NX/NY/NZ107101134
NX/NY/NZ14113986
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-24.53642.554-0.000

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Supplemental data

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Sample components

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Entire : Structure of the Human Secretory Immunoglobulin M Core

EntireName: Structure of the Human Secretory Immunoglobulin M Core
Components
  • Complex: Structure of the Human Secretory Immunoglobulin M Core
    • Protein or peptide: Polymeric immunoglobulin receptor
    • Protein or peptide: Immunoglobulin heavy constant mu
    • Protein or peptide: Immunoglobulin J chain

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Supramolecule #1: Structure of the Human Secretory Immunoglobulin M Core

SupramoleculeName: Structure of the Human Secretory Immunoglobulin M Core
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
Molecular weightTheoretical: 480 kDa/nm

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Macromolecule #1: Polymeric immunoglobulin receptor

MacromoleculeName: Polymeric immunoglobulin receptor / type: protein_or_peptide / ID: 1 / 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 #2: Immunoglobulin heavy constant mu

MacromoleculeName: Immunoglobulin heavy constant mu / type: protein_or_peptide / ID: 2 / Number of copies: 10 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.677605 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DYKDDDDKLE VLFQGPGSLP VIAELPPKVS VFVPPRDGFF GNPRKSKLIC QATGFSPRQI QVSWLREGKQ VGSGVTTDQV QAEAKESGP TTYKVTSTLT IKESDWLGQS MFTCRVDHRG LTFQQNASSM CVPDQDTAIR VFAIPPSFAS IFLTKSTKLT C LVTDLTTY ...String:
DYKDDDDKLE VLFQGPGSLP VIAELPPKVS VFVPPRDGFF GNPRKSKLIC QATGFSPRQI QVSWLREGKQ VGSGVTTDQV QAEAKESGP TTYKVTSTLT IKESDWLGQS MFTCRVDHRG LTFQQNASSM CVPDQDTAIR VFAIPPSFAS IFLTKSTKLT C LVTDLTTY DSVTISWTRQ NGEAVKTHTN ISESHPNATF SAVGEASICE DDWNSGERFT CTVTHTDLPS PLKQTISRPK GV ALHRPDV YLLPPAREQL NLRESATITC LVTGFSPADV FVQWMQRGQP LSPEKYVTSA PMPEPQAPGR YFAHSILTVS EEE WNTGET YTCVVAHEAL PNRVTERTVD KSTGKPTLYN VSLVMSDTAG TCY

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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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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.2 mg/mL
BufferpH: 7.2
Component:
ConcentrationFormulaName
0.02 MHEPESHEPES
0.15 MNaClSodium chloridesodium chloride
GridModel: UltrAuFoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 2.5 nm / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
Details: Blot for 3.5 seconds before plunging with blot force 7..
DetailsSample was monodisperse.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 165000
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: 0.2 sec. / Average electron dose: 1.02 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: CTFFIND (ver. 4)
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cisTEM
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 244123

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