5KNM

Human leukocyte antigen F (HLA-F) presents peptides and regulates immunity through interactions with NK-cell receptors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.303 
  • R-Value Observed: 0.305 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.

Dulberger, C.L.McMurtrey, C.P.Holzemer, A.Neu, K.E.Liu, V.Steinbach, A.M.Garcia-Beltran, W.F.Sulak, M.Jabri, B.Lynch, V.J.Altfeld, M.Hildebrand, W.H.Adams, E.J.

(2017) Immunity 46: 1018-1029.e7

  • DOI: https://doi.org/10.1016/j.immuni.2017.06.002
  • Primary Citation of Related Structures:  
    5IUE, 5KNM

  • PubMed Abstract: 

    Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement. Our in vitro studies confirm that NKRs differentiate between peptide-bound and peptide-free HLA-F. The complex structure of peptide-loaded β 2 m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as β 2 m, thus precluding binding to HLA-F OCs. These findings provide a biochemical framework to understand how HLA-F could regulate immunity via interactions with NKRs.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cDNA FLJ39643 fis, clone SMINT2004023, highly similar to HLA class I histocompatibility antigen, alphachain F284Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P30511 (Homo sapiens)
Explore P30511 
Go to UniProtKB:  P30511
PHAROS:  P30511
GTEx:  ENSG00000204642 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP30511
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin182Homo 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
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Leukocyte immunoglobulin-like receptor subfamily B member 1C [auth D]267Homo sapiensMutation(s): 0 
Gene Names: LILRB1ILT2LIR1MIR7
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NHL6 (Homo sapiens)
Explore Q8NHL6 
Go to UniProtKB:  Q8NHL6
PHAROS:  Q8NHL6
Entity Groups  
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UniProt GroupQ8NHL6
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  • Reference Sequence

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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide ILE-LEU-ARG-TRP-GLU-GLND [auth N]6Trichoplusia niMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.303 
  • R-Value Observed: 0.305 
  • Space Group: P 6 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 231.82α = 90
b = 231.82β = 90
c = 73.25γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
xia2data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01 AI073922

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-14
    Type: Initial release
  • Version 1.1: 2017-07-05
    Changes: Database references
  • Version 1.2: 2017-09-27
    Changes: Author supporting evidence
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Refinement description, Structure summary