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- EMDB-37936: Cryo-EM structure of human CD5L bound to IgM-Fc/J -

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Basic information

Entry
Database: EMDB / ID: EMD-37936
TitleCryo-EM structure of human CD5L bound to IgM-Fc/J
Map data
Sample
  • Complex: Ternary complex of IgM-Fc with the J chain and CD5L
    • Protein or peptide: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
    • Protein or peptide: Immunoglobulin J chain
    • Protein or peptide: Interleukin-2,CD5 antigen-like
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
Keywordsimmunoglobulin / CD5 antigen-like / pentamer / IMMUNE SYSTEM
Function / homology
Function and homology information


positive regulation of complement-dependent cytotoxicity / hexameric IgM immunoglobulin complex / kappa-type opioid receptor binding / regulation of T cell homeostatic proliferation / IgM B cell receptor complex / regulation of CD4-positive, alpha-beta T cell proliferation / dimeric IgA immunoglobulin complex / interleukin-2 receptor binding / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex ...positive regulation of complement-dependent cytotoxicity / hexameric IgM immunoglobulin complex / kappa-type opioid receptor binding / regulation of T cell homeostatic proliferation / IgM B cell receptor complex / regulation of CD4-positive, alpha-beta T cell proliferation / dimeric IgA immunoglobulin complex / interleukin-2 receptor binding / secretory dimeric IgA immunoglobulin complex / pentameric IgM immunoglobulin complex / monomeric IgA immunoglobulin complex / response to tacrolimus / secretory IgA immunoglobulin complex / positive regulation of plasma cell differentiation / glycosphingolipid binding / negative regulation of lymphocyte proliferation / negative regulation of T-helper 17 cell differentiation / positive regulation of tissue remodeling / IgA binding / pre-B cell allelic exclusion / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / IgM immunoglobulin complex / glomerular filtration / regulation of complement activation / leukocyte activation involved in immune response / positive regulation of isotype switching to IgG isotypes / interleukin-2-mediated signaling pathway / activated T cell proliferation / CD22 mediated BCR regulation / kinase activator activity / positive regulation of regulatory T cell differentiation / natural killer cell activation / : / negative regulation of B cell apoptotic process / zymogen activation / Interleukin-2 signaling / positive regulation of immunoglobulin production / positive regulation of dendritic spine development / immune system process / immunoglobulin complex, circulating / immunoglobulin receptor binding / positive regulation of activated T cell proliferation / positive regulation of respiratory burst / positive regulation of interleukin-17 production / humoral immune response / T cell differentiation / Interleukin receptor SHC signaling / cellular defense response / Scavenging of heme from plasma / complement activation, classical pathway / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of B cell proliferation / extrinsic apoptotic signaling pathway in absence of ligand / antigen binding / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / negative regulation of protein phosphorylation / cytokine activity / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / growth factor activity / negative regulation of inflammatory response / positive regulation of inflammatory response / positive regulation of type II interferon production / antibacterial humoral response / cell-cell signaling / protein-macromolecule adaptor activity / positive regulation of cytosolic calcium ion concentration / RAF/MAP kinase cascade / carbohydrate binding / positive regulation of cell growth / protein-containing complex assembly / defense response to Gram-negative bacterium / response to ethanol / blood microparticle / adaptive immune response / Potential therapeutics for SARS / transcription by RNA polymerase II / cell adhesion / inflammatory response / immune response / serine-type endopeptidase activity / innate immune response / positive regulation of cell population proliferation / negative regulation of apoptotic process / apoptotic process / cell surface / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / extracellular region / plasma membrane / cytoplasm
Similarity search - Function
: / SRCR domain signature. / Scavenger receptor cysteine-rich domain / Interleukin-2 / Interleukin-2, conserved site / : / Interleukin 2 / Interleukin-2 signature. / Interleukin-2 family / Immunoglobulin J chain ...: / SRCR domain signature. / Scavenger receptor cysteine-rich domain / Interleukin-2 / Interleukin-2, conserved site / : / Interleukin 2 / Interleukin-2 signature. / Interleukin-2 family / Immunoglobulin J chain / Immunoglobulin J chain / SRCR domain / SRCR domain profile. / SRCR-like domain / SRCR-like domain superfamily / Scavenger receptor Cys-rich / Four-helical cytokine-like, core / : / 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
CD5 antigen-like / Immunoglobulin J chain / Immunoglobulin heavy constant mu / Interleukin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.39 Å
AuthorsWang YX / Su C / Xiao JY
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2024
Title: CD5L associates with IgM via the J chain.
Authors: Yuxin Wang / Chen Su / Chenggong Ji / Junyu Xiao /
Abstract: CD5 antigen-like (CD5L), also known as Spα or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying ...CD5 antigen-like (CD5L), also known as Spα or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying the interaction between IgM and CD5L has remained elusive. In this study, we present a cryo-electron microscopy structure of the human IgM pentamer core in complex with CD5L. Our findings reveal that CD5L binds to the joining chain (J chain) in a Ca-dependent manner and further links to IgM via a disulfide bond. We further corroborate recently published data that CD5L reduces IgM binding to the mucosal transport receptor pIgR, but does not impact the binding of the IgM-specific receptor FcμR. Additionally, CD5L does not interfere with IgM-mediated complement activation. These results offer a more comprehensive understanding of IgM and shed light on the function of the J chain in the immune system.
History
DepositionOct 31, 2023-
Header (metadata) releaseOct 9, 2024-
Map releaseOct 9, 2024-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_37936.png

Downloads & links

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Map

FileDownload / File: emd_37936.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 400 pix.
= 332. Å		0.83 Å/pix.
x 400 pix.
= 332. Å		0.83 Å/pix.
x 400 pix.
= 332. Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.17
Minimum - Maximum-0.98900706 - 1.5423284
Average (Standard dev.)0.00053189986 (±0.028916998)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 332.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_37936_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_37936_half_map_2.map
Projections & Slices
AxesZYX

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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 CD5L

EntireName: Ternary complex of IgM-Fc with the J chain and CD5L
Components
  • Complex: Ternary complex of IgM-Fc with the J chain and CD5L
    • Protein or peptide: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
    • Protein or peptide: Immunoglobulin J chain
    • Protein or peptide: Interleukin-2,CD5 antigen-like
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION

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Supramolecule #1: Ternary complex of IgM-Fc with the J chain and CD5L

SupramoleculeName: Ternary complex of IgM-Fc with the J chain and CD5L / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu

MacromoleculeName: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
type: protein_or_peptide / ID: 1
Details: Signal peptide from Interleukin-2,Immunoglobulin heavy constant mu
Number of copies: 10 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 44.086461 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MYRMQLLSCI ALSLALVTNS ASAWSHPQFE KGGGSGGGSG GSAWSHPQFE KIDTTIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGF SPRQIQVSWL REGKQVGSGV TTDQVQAEAK ESGPTTYKVT STLTIKESDW LGQSMFTCRV DHRGLTFQQN A SSMCVPDQ ...String:
MYRMQLLSCI ALSLALVTNS ASAWSHPQFE KGGGSGGGSG GSAWSHPQFE KIDTTIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGF SPRQIQVSWL REGKQVGSGV TTDQVQAEAK ESGPTTYKVT STLTIKESDW LGQSMFTCRV DHRGLTFQQN A SSMCVPDQ DTAIRVFAIP PSFASIFLTK STKLTCLVTD LTTYDSVTIS WTRQNGEAVK THTNISESHP NATFSAVGEA SI CEDDWNS GERFTCTVTH TDLPSPLKQT ISRPKGVALH RPDVYLLPPA REQLNLRESA TITCLVTGFS PADVFVQWMQ RGQ PLSPEK YVTSAPMPEP QAPGRYFAHS ILTVSEEEWN TGETYTCVVA HEALPNRVTE RTVDKSTGKP TLYNVSLVMS DTAG TCY

UniProtKB: Interleukin-2, Immunoglobulin heavy constant mu

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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: 19.204727 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MKNHLLFWGV LAVFIKAVHV KAQEDERIVL VDNKCKCARI TSRIIRSSED PNEDIVERNI RIIVPLNNRE NISDPTSPLR TRFVYHLSD LCKKCDPTEV ELDNQIVTAT QSNICDEDSA TETCYTYDRN KCYTAVVPLV YGGETKMVET ALTPDACYPD Y PYDVPDYA

UniProtKB: Immunoglobulin J chain

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Macromolecule #3: Interleukin-2,CD5 antigen-like

MacromoleculeName: Interleukin-2,CD5 antigen-like / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.757547 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MYRMQLLSCI ALSLALVTNS ARIHHHHHHH HSPSGVRLVG GLHRCEGRVE VEQKGQWGTV CDDGWDIKDV AVLCRELGCG AASGTPSGI LYEPPAEKEQ KVLIQSVSCT GTEDTLAQCE QEEVYDCSHD EDAGASCENP ESSFSPVPEG VRLADGPGHC K GRVEVKHQ ...String:
MYRMQLLSCI ALSLALVTNS ARIHHHHHHH HSPSGVRLVG GLHRCEGRVE VEQKGQWGTV CDDGWDIKDV AVLCRELGCG AASGTPSGI LYEPPAEKEQ KVLIQSVSCT GTEDTLAQCE QEEVYDCSHD EDAGASCENP ESSFSPVPEG VRLADGPGHC K GRVEVKHQ NQWYTVCQTG WSLRAAKVVC RQLGCGRAVL TQKRCNKHAY GRKPIWLSQM SCSGREATLQ DCPSGPWGKN TC NHDEDTW VECEDPFDLR LVGGDNLCSG RLEVLHKGVW GSVCDDNWGE KEDQVVCKQL GCGKSLSPSF RDRKCYGPGV GRI WLDNVR CSGEEQSLEQ CQHRFWGFHD CTHQEDVAVI CSG

UniProtKB: Interleukin-2, CD5 antigen-like

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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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Macromolecule #6: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: OTHER / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 381470
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

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