5J6G

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

Summary for 5J6G

• Entry DOI: 10.2210/pdb5j6g/pdb
• Related: 5J6H
• Descriptor: H-2 class I histocompatibility antigen, Q10 alpha chain, Beta-2-microglobulin, VAL-GLY-ILE-THR-ASN-VAL-ASP-LEU, ... (4 entities in total)
• Functional Keywords: immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 8
• Total formula weight: 125976.84

Authors

Berry, R.,Rossjohn, J. (deposition date: 2016-04-04, release date: 2016-07-13, Last modification date: 2024-10-23)

Primary citation

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.
Recognition of the Major Histocompatibility Complex (MHC) Class Ib Molecule H2-Q10 by the Natural Killer Cell Receptor Ly49C.
J.Biol.Chem., 291:18740-18752, 2016

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.

PubMed: 27385590
DOI: 10.1074/jbc.M116.737130

Experimental method

X-RAY DIFFRACTION (3.3 Å)