4ZAK

Crystal structure of the mCD1d/DB06-1/iNKTCR ternary complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.82 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-gamma Production.

Birkholz, A.M.Girardi, E.Wingender, G.Khurana, A.Wang, J.Zhao, M.Zahner, S.Illarionov, P.A.Wen, X.Li, M.Yuan, W.Porcelli, S.A.Besra, G.S.Zajonc, D.M.Kronenberg, M.

(2015) J Immunol 195: 924-933

  • DOI: https://doi.org/10.4049/jimmunol.1500070
  • Primary Citation of Related Structures:  
    4ZAK

  • PubMed Abstract: 

    In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with the only change being a single atom: the substitution of a carbonyl oxygen with a sulfur atom. Although DB06-1 is not a more effective Ag in vitro, the small chemical change has a marked impact on the ability of this lipid Ag to stimulate iNKT cells in vivo, with increased IFN-γ production at 24 h compared with αGalCer, increased IL-12, and increased activation of NK cells to produce IFN-γ. These changes are correlated with an enhanced ability of DB06-1 to load in the CD1d molecules expressed by dendritic cells in vivo. Moreover, structural studies suggest a tighter fit into the CD1d binding groove by DB06-1 compared with αGalCer. Surprisingly, when iNKT cells previously exposed to DB06-1 are restimulated weeks later, they have greatly increased IL-10 production. Therefore, our data are consistent with a model whereby augmented and or prolonged presentation of a glycolipid Ag leads to increased activation of NK cells and a Th1-skewed immune response, which may result, in part, from enhanced loading into CD1d. Furthermore, our data suggest that strong antigenic stimulation in vivo may lead to the expansion of IL-10-producing iNKT cells, which could counteract the benefits of increased early IFN-γ production.


  • Organizational Affiliation

    Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92037;


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Antigen-presenting glycoprotein CD1d1285Mus musculusMutation(s): 0 
Gene Names: Cd1d1Cd1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11609 (Mus musculus)
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Go to UniProtKB:  P11609
IMPC:  MGI:107674
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UniProt GroupP11609
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin99Mus musculusMutation(s): 0 
Gene Names: B2m
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Find proteins for P01887 (Mus musculus)
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Go to UniProtKB:  P01887
IMPC:  MGI:88127
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UniProt GroupP01887
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Trav11,Va14Ja18/Vb8.2,Human nkt tcr alpha chain209Mus musculusHomo sapiensMutation(s): 0 
Gene Names: Trav11Trav11dTcr-alphaB2MHDCMA22P
UniProt
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Find proteins for A0A0B4J1J9 (Mus musculus)
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Go to UniProtKB:  A0A0B4J1J9
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UniProt GroupsK7N5M3A0A0B4J1J9A0A0G2JG46
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
T cell antigen receptor beta chain 8.2,T-cell receptor beta-2 chain C region,Protein Trbc2,T-cell receptor beta-2 chain C region241Mus musculusHomo sapiensMutation(s): 2 
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PHAROS:  A0A5B9
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UniProt GroupsA0N8J3A0A5B9A2NTY6
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Oligosaccharides

Help

Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4LX
Query on 4LX

Download Ideal Coordinates CCD File 
H [auth A]N-[(2S,3S,4R)-1-(alpha-D-galactopyranosyloxy)-3,4-dihydroxyoctadecan-2-yl]hexacosanethioamide
C50 H99 N O8 S
MSKBSPRYFRAUPB-BYSUZVQFSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.82 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.921α = 90
b = 190.544β = 90
c = 150.76γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
Blu-Icedata collection
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI074952

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-01
    Type: Initial release
  • Version 1.1: 2015-07-29
    Changes: Database references
  • Version 1.2: 2017-09-06
    Changes: Author supporting evidence, Derived calculations, Source and taxonomy
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-09-27
    Changes: Data collection, Database references, Refinement description, Structure summary