5W1V

Structure of the HLA-E-VMAPRTLIL/GF4 TCR complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.31 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct alpha beta T cell receptors.

Sullivan, L.C.Walpole, N.G.Farenc, C.Pietra, G.Sum, M.J.W.Clements, C.S.Lee, E.J.Beddoe, T.Falco, M.Mingari, M.C.Moretta, L.Gras, S.Rossjohn, J.Brooks, A.G.

(2017) J Biol Chem 292: 21149-21158

  • DOI: https://doi.org/10.1074/jbc.M117.807719
  • Primary Citation of Related Structures:  
    5W1V, 5W1W

  • PubMed Abstract: 

    αβ T cell receptors (TCRs) interact with peptides bound to the polymorphic major histocompatibility complex class Ia (MHC-Ia) and class II (MHC-II) molecules as well as the essentially monomorphic MHC class Ib (MHC-Ib) molecules. Although there is a large amount of information on how TCRs engage with MHC-Ia and MHC-II, our understanding of TCR/MHC-Ib interactions is very limited. Infection with cytomegalovirus (CMV) can elicit a CD8 + T cell response restricted by the human MHC-Ib molecule human leukocyte antigen (HLA)-E and specific for an epitope from UL40 (VMAPRTLIL), which is characterized by biased TRBV14 gene usage. Here we describe an HLA-E-restricted CD8 + T cell able to recognize an allotypic variant of the UL40 peptide with a modification at position 8 (P8) of the peptide (VMAPRTLVL) that uses the TRBV9 gene segment. We report the structures of a TRBV9 + TCR in complex with the HLA-E molecule presenting the two peptides. Our data revealed that the TRBV9 + TCR adopts a different docking mode and molecular footprint atop HLA-E when compared with the TRBV14 + TCR-HLA-E ternary complex. Additionally, despite their differing V gene segment usage and different docking mechanisms, mutational analyses showed that the TCRs shared a conserved energetic footprint on the HLA-E molecule, focused around the peptide-binding groove. Hence, we provide new insights into how monomorphic MHC molecules interact with T cells.


  • Organizational Affiliation

    From the Department of Microbiology and Immunology and Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3000, Australia.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, alpha chain E
A, F, K, P
278Homo sapiensMutation(s): 0 
Gene Names: HLA-EHLA-6.2HLAE
UniProt & NIH Common Fund Data Resources
Find proteins for P13747 (Homo sapiens)
Explore P13747 
Go to UniProtKB:  P13747
PHAROS:  P13747
GTEx:  ENSG00000204592 
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UniProt GroupP13747
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, G, L, Q
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
VMAPRTLIL peptide from CMV gpUL40
C, H, M, R
9Human herpesvirus 5 strain AD169Mutation(s): 0 
Gene Names: UL40
UniProt
Find proteins for P16780 (Human cytomegalovirus (strain AD169))
Explore P16780 
Go to UniProtKB:  P16780
Entity Groups  
UniProt GroupP16780
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
GF4 T cell receptor alpha chain
D, I, N, S
207Homo sapiensMutation(s): 0 
Gene Names: TRAC TCRA
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  • Reference Sequence
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
GF4 T cell receptor beta chain
E, J, O, T
246Homo sapiensMutation(s): 0 
Gene Names: TRBC1
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.31 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.646α = 90
b = 228.246β = 90
c = 276.872γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

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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: 2017-10-04
    Type: Initial release
  • Version 1.1: 2017-10-18
    Changes: Database references
  • Version 1.2: 2018-01-03
    Changes: Database references
  • Version 1.3: 2018-01-17
    Changes: Author supporting evidence
  • Version 1.4: 2020-01-01
    Changes: Author supporting evidence