6C09

Ternary crystal structure of the 3C8 TCR-CD1c-monoacylglycerol complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.

Wun, K.S.Reijneveld, J.F.Cheng, T.Y.Ladell, K.Uldrich, A.P.Le Nours, J.Miners, K.L.McLaren, J.E.Grant, E.J.Haigh, O.L.Watkins, T.S.Suliman, S.Iwany, S.Jimenez, J.Calderon, R.Tamara, K.L.Leon, S.R.Murray, M.B.Mayfield, J.A.Altman, J.D.Purcell, A.W.Miles, J.J.Godfrey, D.I.Gras, S.Price, D.A.Van Rhijn, I.Moody, D.B.Rossjohn, J.

(2018) Nat Immunol 19: 397-406

  • DOI: https://doi.org/10.1038/s41590-018-0065-7
  • Primary Citation of Related Structures:  
    6C09, 6C15

  • PubMed Abstract: 

    The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.


  • Organizational Affiliation

    Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
T-cell surface glycoprotein CD1c287Homo sapiensMutation(s): 0 
Gene Names: CD1C
UniProt & NIH Common Fund Data Resources
Find proteins for P29017 (Homo sapiens)
Explore P29017 
Go to UniProtKB:  P29017
PHAROS:  P29017
GTEx:  ENSG00000158481 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29017
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin108Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61769
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
3C8 T cell receptor alpha-chain205Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
3C8 T cell receptor beta-chain247Homo sapiensMutation(s): 0 
Entity Groups  
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  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EKG
Query on EKG

Download Ideal Coordinates CCD File 
F [auth A](2R)-2,3-dihydroxypropyl hexadecanoate
C19 H38 O4
QHZLMUACJMDIAE-GOSISDBHSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
D10
Query on D10

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A]
DECANE
C10 H22
DIOQZVSQGTUSAI-UHFFFAOYSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
N [auth C]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
K [auth C],
L [auth C],
M [auth C]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
O [auth D]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 173.17α = 90
b = 173.17β = 90
c = 82.47γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)Australia--
Australian Research Council (ARC)Australia--

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-21
    Type: Initial release
  • Version 1.1: 2018-03-28
    Changes: Data collection, Database references, Source and taxonomy
  • Version 1.2: 2018-04-04
    Changes: Data collection, Database references
  • Version 1.3: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2023-10-04
    Changes: Data collection, Database references, Refinement description, Structure summary