6D2T

HLA-B*57:01 presenting LALLTGVRW


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands.

Faridi, P.Li, C.Ramarathinam, S.H.Vivian, J.P.Illing, P.T.Mifsud, N.A.Ayala, R.Song, J.Gearing, L.J.Hertzog, P.J.Ternette, N.Rossjohn, J.Croft, N.P.Purcell, A.W.

(2018) Sci Immunol 3

  • DOI: https://doi.org/10.1126/sciimmunol.aar3947
  • Primary Citation of Related Structures:  
    6D29, 6D2B, 6D2R, 6D2T

  • PubMed Abstract: 

    The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy.


  • Organizational Affiliation

    Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, B-57 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
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
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
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
LEU-ALA-LEU-LEU-THR-GLY-VAL-ARG-TRP9synthetic constructMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.686α = 90
b = 82.1β = 90
c = 109.842γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-03
    Type: Initial release
  • Version 1.1: 2019-04-17
    Changes: Data collection, Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description