5J6G

Recognition of the MHC class Ib molecule H2-Q10 by the natural killer cell receptor Ly49C


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Recognition of the Major Histocompatibility Complex (MHC) Class Ib Molecule H2-Q10 by the Natural Killer Cell Receptor Ly49C.

Sullivan, L.C.Berry, R.Sosnin, N.Widjaja, J.M.Deuss, F.A.Balaji, G.R.LaGruta, N.L.Mirams, M.Trapani, J.A.Rossjohn, J.Brooks, A.G.Andrews, D.M.

(2016) J Biol Chem 291: 18740-18752

  • DOI: https://doi.org/10.1074/jbc.M116.737130
  • Primary Citation of Related Structures:  
    5J6G, 5J6H

  • PubMed Abstract: 

    Murine natural killer (NK) cells are regulated by the interaction of Ly49 receptors with major histocompatibility complex class I molecules (MHC-I). Although the ligands for inhibitory Ly49 were considered to be restricted to classical MHC (MHC-Ia), we have shown that the non-classical MHC molecule (MHC-Ib) H2-M3 was a ligand for the inhibitory Ly49A. Here we establish that another MHC-Ib, H2-Q10, is a bona fide ligand for the inhibitory Ly49C receptor. H2-Q10 bound to Ly49C with a marginally lower affinity (∼5 μm) than that observed between Ly49C and MHC-Ia (H-2K(b)/H-2D(d), both ∼1 μm), and this recognition could be prevented by cis interactions with H-2K in situ To understand the molecular details underpinning Ly49·MHC-Ib recognition, we determined the crystal structures of H2-Q10 and Ly49C bound H2-Q10. Unliganded H2-Q10 adopted a classical MHC-I fold and possessed a peptide-binding groove that exhibited features similar to those found in MHC-Ia, explaining the diverse peptide binding repertoire of H2-Q10. Ly49C bound to H2-Q10 underneath the peptide binding platform to a region that encompassed residues from the α1, α2, and α3 domains, as well as the associated β2-microglobulin subunit. This docking mode was conserved with that previously observed for Ly49C·H-2K(b) Indeed, structure-guided mutation of Ly49C indicated that Ly49C·H2-Q10 and Ly49C·H-2K(b) possess similar energetic footprints focused around residues located within the Ly49C β4-stand and L5 loop, which contact the underside of the peptide-binding platform floor. Our data provide a structural basis for Ly49·MHC-Ib recognition and demonstrate that MHC-Ib represent an extended family of ligands for Ly49 molecules.


  • Organizational Affiliation

    From the Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
H-2 class I histocompatibility antigen, Q10 alpha chain
A, C
300Mus musculusMutation(s): 0 
Gene Names: H2-Q10
UniProt & NIH Common Fund Data Resources
Find proteins for P01898 (Mus musculus)
Explore P01898 
Go to UniProtKB:  P01898
IMPC:  MGI:95929
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UniProt GroupP01898
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, D
100Mus musculusMutation(s): 0 
Gene Names: B2m
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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UniProt GroupP01887
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VAL-GLY-ILE-THR-ASN-VAL-ASP-LEU
E, F
8Mus musculusMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9DBG6 (Mus musculus)
Explore Q9DBG6 
Go to UniProtKB:  Q9DBG6
IMPC:  MGI:98085
Entity Groups  
UniProt GroupQ9DBG6
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Killer cell lectin-like receptor 3
G, H
132Mus musculusMutation(s): 0 
Gene Names: Klra3Ly-49cLy49C
UniProt
Find proteins for Q64329 (Mus musculus)
Explore Q64329 
Go to UniProtKB:  Q64329
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UniProt GroupQ64329
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 
  • Space Group: I 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.01α = 90
b = 57.8β = 96.15
c = 210.704γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaGNT1035636
National Health and Medical Research Council (NHMRC, Australia)AustraliaGNT1109901

Revision History  (Full details and data files)

  • Version 1.0: 2016-07-13
    Type: Initial release
  • Version 1.1: 2016-07-20
    Changes: Database references
  • Version 1.2: 2016-09-14
    Changes: Database references
  • Version 1.3: 2017-09-20
    Changes: Author supporting evidence, Data collection, Database references, Derived calculations
  • Version 1.4: 2020-01-08
    Changes: Author supporting evidence