5D2N

Crystal structure of C25-NLV-HLA-A2 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural Basis for Clonal Diversity of the Public T Cell Response to a Dominant Human Cytomegalovirus Epitope.

Yang, X.Gao, M.Chen, G.Pierce, B.G.Lu, J.Weng, N.P.Mariuzza, R.A.

(2015) J Biol Chem 290: 29106-29119

  • DOI: https://doi.org/10.1074/jbc.M115.691311
  • Primary Citation of Related Structures:  
    5D2L, 5D2N

  • PubMed Abstract: 

    Cytomegalovirus (CMV) is a ubiquitous and persistent human pathogen that is kept in check by CD8(+) cytotoxic T lymphocytes. Individuals expressing the major histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant CMV epitope NLVPMVATV (NLV). The NLV-specific T cell repertoire is characterized by a high prevalence of TCRs that are frequently observed in multiple unrelated individuals. These public TCRs feature identical, or nearly identical, complementarity-determining region 3α (CDR3α) and/or CDR3β sequences. The TCRs may express public CDR3α motifs alone, public CDR3β motifs alone, or dual public CDR3αβ motifs. In addition, the same public CDR3α motif may pair with different CDR3β motifs (and the reverse), giving rise to highly diverse NLV-specific TCR repertoires. To investigate the structural underpinnings of this clonal diversity, we determined crystal structures of two public TCRs (C7 and C25) in complex with NLV·HLA-A2. These TCRs utilize completely different CDR3α and CDR3β motifs that, in addition, can associate with multiple variable α and variable β regions in NLV-specific T cell repertoires. The C7·NLV·HLA-A2 and C25·NLV·HLA-A2 complexes exhibit divergent TCR footprints on peptide-MHC such that C25 is more focused on the central portion of the NLV peptide than is C7. These structures combined with molecular modeling show how the public CDR3α motif of C25 may associate with different variable α regions and how the public CDR3α motif of C7 may pair with different CDR3β motifs. This interchangeability of TCR V regions and CDR3 motifs permits multiple structural solutions to binding an identical peptide-MHC ligand and thereby the generation of a clonally diverse public T cell response to CMV.


  • Organizational Affiliation

    From the University of Maryland Institute for Bioscience and Biotechnology Research, W. M. Keck Laboratory for Structural Biology, Rockville, Maryland 20850, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C25 alphaA [auth C],
E [auth D]
203Homo sapiensMutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C25 betaB [auth F],
F [auth E]
247Homo sapiensMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chainC [auth H],
G [auth A]
276Homo sapiensMutation(s): 0 
Gene Names: HLA-AHLAA
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
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Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
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UniProt GroupP04439
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulinD [auth L],
H [auth B]
100Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
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PHAROS:  P61769
GTEx:  ENSG00000166710 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
ASN-LEU-VAL-PRO-MET-VAL-ALA-THR-VALI [auth G],
J [auth I]
9CytomegalovirusMutation(s): 0 
UniProt
Find proteins for P18139 (Human cytomegalovirus (strain Towne))
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Go to UniProtKB:  P18139
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UniProt GroupP18139
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.307α = 90
b = 124.874β = 90
c = 193.843γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI036900

Revision History  (Full details and data files)

  • Version 1.0: 2015-10-07
    Type: Initial release
  • Version 1.1: 2017-09-27
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.2: 2019-05-08
    Changes: Data collection, Derived calculations
  • Version 1.3: 2019-11-13
    Changes: Database references
  • Version 1.4: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Refinement description