6CYW

Structure of sphingomyelin in complex with mouse CD1d


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.224 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin.

Melum, E.Jiang, X.Baker, K.D.Macedo, M.F.Fritsch, J.Dowds, C.M.Wang, J.Pharo, A.Kaser, A.Tan, C.Pereira, C.S.Kelly, S.L.Duan, J.Karlsen, T.H.Exley, M.A.Schutze, S.Zajonc, D.M.Merrill, A.H.Schuchman, E.H.Zeissig, S.Blumberg, R.S.

(2019) Nat Immunol 20: 1644-1655

  • DOI: https://doi.org/10.1038/s41590-019-0504-0
  • Primary Citation of Related Structures:  
    6CYW

  • PubMed Abstract: 

    Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.


  • Organizational Affiliation

    Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. espen.melum@medisin.uio.no.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Antigen-presenting glycoprotein CD1d1285Mus musculusMutation(s): 0 
Gene Names: Cd1d1mCG_3074
UniProt & NIH Common Fund Data Resources
Find proteins for P11609 (Mus musculus)
Explore P11609 
Go to UniProtKB:  P11609
IMPC:  MGI:107674
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11609
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin99Mus musculusMutation(s): 0 
Gene Names: B2m
UniProt & NIH Common Fund Data Resources
Find proteins for P01887 (Mus musculus)
Explore P01887 
Go to UniProtKB:  P01887
IMPC:  MGI:88127
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01887
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.224 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.134α = 90
b = 105.256β = 90
c = 106.388γ = 90
Software Package:
Software NamePurpose
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-10
    Type: Initial release
  • Version 1.1: 2019-11-27
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description, Structure summary