5J6H: Recognition Of The Mhc Class Ib Molecule H2-q10 By The Natural Killer Cell Receptor Ly49c

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 ( approximately 5 mum) than that observed between Ly49C and MHC-Ia (H-2K(b)/H-2D(d), both approximately 1 mum), 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 alpha1, alpha2, and alpha3 domains, as well as the associated beta2-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 beta4-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.
PDB ID: 5J6HDownload
MMDB ID: 140892
PDB Deposition Date: 2016/4/5
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 5J6H: trimeric; determined by author and by software (PISA)
Molecular Components in 5J6H
Label Count Molecule
Proteins (3 molecules)
H-2 Class I Histocompatibility Antigen, Q10 Alpha Chain(Gene symbol: H2-Q10)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2m)
Molecule annotation
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB