2FO4

Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.193 

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Literature

Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide

Lazoura, E.Lodding, J.Farrugia, W.Ramsland, P.A.Stevens, J.Wilson, I.A.Pietersz, G.A.Apostolopoulos, V.

(2006) Immunology 119: 306-316

  • DOI: https://doi.org/10.1111/j.1365-2567.2006.02434.x
  • Primary Citation of Related Structures:  
    2FO4

  • PubMed Abstract: 

    Designing peptide-based vaccines for therapeutic applications in cancer immunotherapy requires detailed knowledge of the interactions between the antigenic peptide and major histocompatibility complex (MHC) in addition to that between the peptide-MHC complex and the T-cell receptor. Past efforts to immunize with high-affinity tumour-associated antigenic peptides have not been very immunogenic, which may be attributed to the lack of T cells to these peptides, having been deleted during thymic development. For this reason, low-to-medium affinity non-canonical peptides represent more suitable candidates. However, in addition to the difficulty in identifying such antigens, peptide binding to MHC, and hence its ability to induce a strong immune response, is limited. Therefore, to enhance binding to MHC and improve immune responses, anchor modifications of non-canonical tumour-associated peptides would be advantageous. In this study, the non-canonical tumour-associated peptide from MUC1, MUC1-8 (SAPDTRPA), was modified at the MHC anchor residues to SAPDFRPL (MUC1-8-5F8L) and showed enhanced binding to H-2Kb and improved immune responses. Furthermore, the crystal structure of MUC1-8-5F8L in complex with H-2Kb was determined and it revealed that binding of the peptide to MHC is similar to that of the canonical peptide OVA8 (SIINFEKL).


  • Organizational Affiliation

    Burnet Institute at Austin, Immunology and Vaccine Laboratory, Heidelberg, VIC, Australia. eliadalzoura@hotmail.com


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
H-2 class I histocompatibility antigen, K-B alpha chain274Mus musculusMutation(s): 0 
UniProt
Find proteins for Q3UBW0 (Mus musculus)
Explore Q3UBW0 
Go to UniProtKB:  Q3UBW0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ3UBW0
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin99Mus musculusMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01887 (Mus musculus)
Explore P01887 
Go to UniProtKB:  P01887
IMPC:  MGI:88127
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01887
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
8-mer from Mucin-1C [auth P]8N/AMutation(s): 2 
UniProt & NIH Common Fund Data Resources
Find proteins for P15941 (Homo sapiens)
Explore P15941 
Go to UniProtKB:  P15941
PHAROS:  P15941
GTEx:  ENSG00000185499 
Entity Groups  
UniProt GroupP15941
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranoseD [auth C]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G86851RC
GlyCosmos:  G86851RC
GlyGen:  G86851RC
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.193 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135.26α = 90
b = 87.89β = 90
c = 45.16γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-14
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2021-11-10
    Changes: Database references, Structure summary
  • Version 2.2: 2023-10-25
    Changes: Data collection, Refinement description