3BHB

Crystal Structure of KMD Phosphopeptide Bound to Human Class I MHC HLA-A2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.226 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self

Mohammed, F.Cobbold, M.Zarling, A.L.Salim, M.Barrett-Wilt, G.A.Shabanowitz, J.Hunt, D.F.Engelhard, V.H.Willcox, B.E.

(2008) Nat Immunol 9: 1236-1243

  • DOI: https://doi.org/10.1038/ni.1660
  • Primary Citation of Related Structures:  
    3BGM, 3BH8, 3BH9, 3BHB

  • PubMed Abstract: 

    Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphopeptides on cancer cells provides an immunological signature of 'transformed self'. Here we demonstrate that phosphorylation can considerably increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide-HLA-A2 complexes. These identified a novel peptide-binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting binding to major histocompatibility complex molecules or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.


  • Organizational Affiliation

    Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chain274Homo sapiensMutation(s): 0 
Gene Names: HLA-AHLAA
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
Explore P04439 
Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04439
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin98Homo sapiensMutation(s): 0 
Gene Names: B2M
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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UniProt GroupP61769
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
decameric peptide from NEDD4-binding protein 210N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q86UW6 (Homo sapiens)
Explore Q86UW6 
Go to UniProtKB:  Q86UW6
PHAROS:  Q86UW6
GTEx:  ENSG00000078177 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ86UW6
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
C
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.226 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.1α = 90
b = 80.2β = 115.9
c = 57.3γ = 90
Software Package:
Software NamePurpose
XSCALEdata processing
CNSrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
XSCALEdata scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance