6W9V

Structure of human MAIT A-F7 TCR in complex with patient MR1-R9H without ligand


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.163 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1 .

Howson, L.J.Awad, W.von Borstel, A.Lim, H.J.McWilliam, H.E.G.Sandoval-Romero, M.L.Majumdar, S.Hamzeh, A.R.Andrews, T.D.McDermott, D.H.Murphy, P.M.Le Nours, J.Mak, J.Y.W.Liu, L.Fairlie, D.P.McCluskey, J.Villadangos, J.A.Cook, M.C.Turner, S.J.Davey, M.S.Ojaimi, S.Rossjohn, J.

(2020) Sci Immunol 5

  • DOI: https://doi.org/10.1126/sciimmunol.abc9492
  • Primary Citation of Related Structures:  
    6W9U, 6W9V

  • PubMed Abstract: 

    The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1 R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1 R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1 R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.


  • Organizational Affiliation

    Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. jamie.rossjohn@monash.edu lauren.howson@monash.edu.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Major histocompatibility complex class I-related gene protein
A, C
271Homo sapiensMutation(s): 1 
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  
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UniProt GroupQ95460
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, F
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 
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UniProt GroupP61769
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
TCR-alpha chain
D, G
204Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
TCR-beta chain
E, H
246Homo sapiensMutation(s): 0 
Entity Groups  
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.163 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 216.99α = 90
b = 70.405β = 104.152
c = 142.901γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


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

Revision History  (Full details and data files)

  • Version 1.0: 2020-08-05
    Type: Initial release
  • Version 1.1: 2020-09-30
    Changes: Database references
  • Version 1.2: 2023-10-18
    Changes: Data collection, Database references, Refinement description