4QRQ

Crystal Structure of HLA B*0801 in complex with HSKKKCDEL


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

An Extensive Antigenic Footprint Underpins Immunodominant TCR Adaptability against a Hypervariable Viral Determinant.

Nivarthi, U.K.Gras, S.Kjer-Nielsen, L.Berry, R.Lucet, I.S.Miles, J.J.Tracy, S.L.Purcell, A.W.Bowden, D.S.Hellard, M.Rossjohn, J.McCluskey, J.Bharadwaj, M.

(2014) J Immunol 193: 5402-5413

  • DOI: https://doi.org/10.4049/jimmunol.1401357
  • Primary Citation of Related Structures:  
    4QRP, 4QRQ

  • PubMed Abstract: 

    Mutations in T cell epitopes are implicated in hepatitis C virus (HCV) persistence and can impinge on vaccine development. We recently demonstrated a narrow bias in the human TCR repertoire targeted at an immunodominant, but highly mutable, HLA-B*0801-restricted epitope ((1395)HSKKKCDEL(1403) [HSK]). To investigate if the narrow TCR repertoire facilitates CTL escape, structural and biophysical studies were undertaken, alongside comprehensive functional analysis of T cells targeted at the natural variants of HLA-B*0801-HSK in different HCV genotypes and quasispecies. Interestingly, within the TCR-HLA-B*0801-HSK complex, the TCR contacts all available surface-exposed residues of the HSK determinant. This broad epitope coverage facilitates cross-genotypic reactivity and recognition of common mutations reported in HCV quasispecies, albeit to a varying degree. Certain mutations did abrogate T cell reactivity; however, natural variants comprising these mutations are reportedly rare and transient in nature, presumably due to fitness costs. Overall, despite a narrow bias, the TCR accommodated frequent mutations by acting like a blanket over the hypervariable epitope, thereby providing effective viral immunity. Our findings simultaneously advance the understanding of anti-HCV immunity and indicate the potential for cross-genotype HCV vaccines.


  • Organizational Affiliation

    Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3000, Australia;


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, B-8 alpha chain276Homo sapiensMutation(s): 0 
Gene Names: HLA-BHLAB
UniProt & NIH Common Fund Data Resources
Find proteins for P01889 (Homo sapiens)
Explore P01889 
Go to UniProtKB:  P01889
PHAROS:  P01889
GTEx:  ENSG00000234745 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01889
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin100Homo 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

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
NS3-4A protein9Hepacivirus hominisMutation(s): 0 
UniProt
Find proteins for X2G898 (Hepacivirus hominis)
Explore X2G898 
Go to UniProtKB:  X2G898
Entity Groups  
UniProt GroupX2G898
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.183 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.836α = 90
b = 81.511β = 90
c = 110.789γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-11-12
    Type: Initial release
  • Version 1.1: 2014-12-24
    Changes: Database references
  • Version 1.2: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.3: 2020-09-16
    Changes: Database references, Structure summary
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Refinement description