6XQP

Structure of human D462-E4 TCR in complex with human MR1-5-OP-RU


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Atypical TRAV1-2 - T cell receptor recognition of the antigen-presenting molecule MR1.

Awad, W.Meermeier, E.W.Sandoval-Romero, M.L.Le Nours, J.Worley, A.H.Null, M.D.Liu, L.McCluskey, J.Fairlie, D.P.Lewinsohn, D.M.Rossjohn, J.

(2020) J Biol Chem 295: 14445-14457

  • DOI: https://doi.org/10.1074/jbc.RA120.015292
  • Primary Citation of Related Structures:  
    6XQP, 6XQQ

  • PubMed Abstract: 

    MR1 presents vitamin B-related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2 + αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2 - MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2 - TCRs interact with MR1-antigen complexes remains unclear. Here, we describe how a TRAV12-2 + TCR (termed D462-E4) recognizes an MR1-antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F'-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F'-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A'-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2 + and TRAV36 + TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.


  • Organizational Affiliation

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


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Major histocompatibility complex class I-related gene protein
A, C
271Homo sapiensMutation(s): 0 
Gene Names: MR1
UniProt & NIH Common Fund Data Resources
Find proteins for Q95460 (Homo sapiens)
Explore Q95460 
Go to UniProtKB:  Q95460
PHAROS:  Q95460
GTEx:  ENSG00000153029 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ95460
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, D
100Homo 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
TRAV12-2 alpha chain
E, G
205Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
TRBV29-1
F, H
248Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2LJ (Subject of Investigation/LOI)
Query on 2LJ

Download Ideal Coordinates CCD File 
I [auth A],
K [auth C]
1-deoxy-1-({2,6-dioxo-5-[(E)-propylideneamino]-1,2,3,6-tetrahydropyrimidin-4-yl}amino)-D-ribitol
C12 H20 N4 O6
YCMPUNANLDFPQG-FHZGFTDOSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
J [auth A]
L [auth C]
M [auth C]
N [auth C]
P [auth F]
J [auth A],
L [auth C],
M [auth C],
N [auth C],
P [auth F],
U [auth H],
V [auth H]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
BR
Query on BR

Download Ideal Coordinates CCD File 
O [auth E],
T [auth G]
BROMIDE ION
Br
CPELXLSAUQHCOX-UHFFFAOYSA-M
CL
Query on CL

Download Ideal Coordinates CCD File 
R [auth F],
S [auth F],
W [auth H],
X [auth H]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
Q [auth F]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.877α = 90
b = 113.433β = 90
c = 209.606γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Australian Research Council (ARC)Australia--

Revision History  (Full details and data files)

  • Version 1.0: 2020-08-26
    Type: Initial release
  • Version 1.1: 2020-09-02
    Changes: Database references
  • Version 1.2: 2020-10-28
    Changes: Database references
  • Version 1.3: 2023-10-18
    Changes: Data collection, Database references, Refinement description