6O53

Structure of HLA-A2:01 with peptide MM96


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Anin silico-in vitroPipeline Identifying an HLA-A*02:01+KRAS G12V+Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients.

Mishto, M.Mansurkhodzhaev, A.Ying, G.Bitra, A.Cordfunke, R.A.Henze, S.Paul, D.Sidney, J.Urlaub, H.Neefjes, J.Sette, A.Zajonc, D.M.Liepe, J.

(2019) Front Immunol 10: 2572-2572

  • DOI: https://doi.org/10.3389/fimmu.2019.02572
  • Primary Citation of Related Structures:  
    6O4Y, 6O4Z, 6O51, 6O53

  • PubMed Abstract: 

    Targeting CD8 + T cells to recurrent tumor-specific mutations can profoundly contribute to cancer treatment. Some of these mutations are potential tumor antigens although they can be displayed by non-spliced epitopes only in a few patients, because of the low affinity of the mutated non-spliced peptides for the predominant HLA class I alleles. Here, we describe a pipeline that uses the large sequence variety of proteasome-generated spliced peptides and identifies spliced epitope candidates, which carry the mutations and bind the predominant HLA-I alleles with high affinity. They could be used in adoptive T cell therapy and other anti-cancer immunotherapies for large cohorts of cancer patients. As a proof of principle, the application of this pipeline led to the identification of a KRAS G12V mutation-carrying spliced epitope candidate, which is produced by proteasomes, transported by TAPs and efficiently presented by the most prevalent HLA class I molecules, HLA-A * 02:01 complexes.


  • Organizational Affiliation

    Centre for Inflammation Biology and Cancer Immunology (CIBCI) & Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MHC class I antigen274Homo sapiensMutation(s): 0 
Gene Names: HLA-A
UniProt
Find proteins for A0A140T913 (Homo sapiens)
Explore A0A140T913 
Go to UniProtKB:  A0A140T913
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A140T913
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin99Homo 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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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61769
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
MM9610Schaalia radingaeMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01116 (Homo sapiens)
Explore P01116 
Go to UniProtKB:  P01116
PHAROS:  P01116
GTEx:  ENSG00000133703 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01116
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.247α = 90
b = 79.638β = 116.12
c = 57.227γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-01-15
    Type: Initial release
  • Version 1.1: 2023-10-11
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description