3WUW

KIR3DL1 in complex with HLA-B*57:01.I80T


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 

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This is version 1.2 of the entry. See complete history


Literature

Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity

O'connor, G.M.Vivian, J.P.Widjaja, J.M.Bridgeman, J.S.Gostick, E.Lafont, B.A.P.Anderson, S.K.Price, D.A.Brooks, A.G.Rossjohn, J.Mcvicar, D.W.

(2014) J Immunol 192: 2875-2884

  • DOI: https://doi.org/10.4049/jimmunol.1303142
  • Primary Citation of Related Structures:  
    3WUW

  • PubMed Abstract: 

    Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation.


  • Organizational Affiliation

    Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702;


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, B-57 alpha chain275Homo sapiensMutation(s): 1 
Gene Names: HLA-BHLA-B*57:01HLAB
UniProt & NIH Common Fund Data Resources
Find proteins for P01889 (Homo sapiens)
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Go to UniProtKB:  P01889
PHAROS:  P01889
GTEx:  ENSG00000234745 
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UniProt GroupP01889
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin98Homo sapiensMutation(s): 0 
Gene Names: B2MBeta 2 MicroglobulinCDABP0092HDCMA22P
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
Peptide9Homo sapiensMutation(s): 0 
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Find proteins for P01834 (Homo sapiens)
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Go to UniProtKB:  P01834
PHAROS:  P01834
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UniProt GroupP01834
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Killer cell immunoglobulin-like receptor 3DL1D [auth G]301Homo sapiensMutation(s): 0 
Gene Names: CD158EKIR3DL1KIR3DL1*001NKAT3NKB1
UniProt & NIH Common Fund Data Resources
Find proteins for P43629 (Homo sapiens)
Explore P43629 
Go to UniProtKB:  P43629
PHAROS:  P43629
GTEx:  ENSG00000167633 
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UniProt GroupP43629
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.058α = 94.66
b = 61.494β = 99.58
c = 66.356γ = 109.14
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-28
    Type: Initial release
  • Version 1.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description, Structure summary