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- PDB-8wys: Local map of human CD5L bound to IgM-Fc/J -

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Basic information

Entry
Database: PDB / ID: 8wys
TitleLocal map of human CD5L bound to IgM-Fc/J
Components
  • Immunoglobulin J chain
  • Interleukin-2,CD5 antigen-like
  • Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
KeywordsIMMUNE SYSTEM / immunoglobulin / CD5 antigen-like / pentamer
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)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å
AuthorsWang, Y.X. / Su, C. / Xiao, J.Y.
Funding support China, 1items
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, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 9, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Category: em_admin / Item: _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
L: Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu
M: Interleukin-2,CD5 antigen-like
J: Immunoglobulin J chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)148,0829
Polymers147,1354
Non-polymers9475
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 3 types, 4 molecules ALMJ

#1: Protein Interleukin-2,Isoform 1 of Immunoglobulin heavy constant mu / IL-2 / T-cell growth factor / TCGF / Ig mu chain C region / Ig mu chain C region BOT / Ig mu chain ...IL-2 / T-cell growth factor / TCGF / Ig mu chain C region / Ig mu chain C region BOT / Ig mu chain C region GAL / Ig mu chain C region OU


Mass: 44086.461 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2, IGHM / Production host: Homo sapiens (human) / References: UniProt: P60568, UniProt: P01871
#2: Protein Interleukin-2,CD5 antigen-like / IL-2 / T-cell growth factor / TCGF / Apoptosis inhibitor expressed by macrophages / hAIM / CT-2 / ...IL-2 / T-cell growth factor / TCGF / Apoptosis inhibitor expressed by macrophages / hAIM / CT-2 / IgM-associated peptide / SP-alpha


Mass: 39757.547 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2, CD5L, API6, UNQ203/PRO229 / Production host: Homo sapiens (human) / References: UniProt: P60568, UniProt: O43866
#3: Protein Immunoglobulin J chain


Mass: 19204.727 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JCHAIN / Production host: Homo sapiens (human) / References: UniProt: P01591

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Sugars , 2 types, 3 molecules

#4: 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.: 1 / Source method: obtained synthetically
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
#5: 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.: 2 / Source method: obtained synthetically / 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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Non-polymers , 1 types, 2 molecules

#6: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationY

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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

ComponentName: Ternary complex of IgM-Fc with the J chain and CD5L / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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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: SPOT SCAN
Electron lensMode: OTHER / Nominal defocus max: 1500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 1.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.20.1_4487: / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 381470 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0166485
ELECTRON MICROSCOPYf_angle_d1.1148841
ELECTRON MICROSCOPYf_dihedral_angle_d5.736894
ELECTRON MICROSCOPYf_chiral_restr0.0551015
ELECTRON MICROSCOPYf_plane_restr0.0091141

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