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PDBsum entry 5j6g
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Immune system
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PDB id
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5j6g
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Contents |
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272 a.a.
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99 a.a.
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122 a.a.
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References listed in PDB file
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Key reference
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Title
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Recognition of the major histocompatibility complex (mhc) class ib molecule h2-Q10 by the natural killer cell receptor ly49c.
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Authors
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L.C.Sullivan,
R.Berry,
N.Sosnin,
J.M.Widjaja,
F.A.Deuss,
G.R.Balaji,
N.L.Lagruta,
M.Mirams,
J.A.Trapani,
J.Rossjohn,
A.G.Brooks,
D.M.Andrews.
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Ref.
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J Biol Chem, 2016,
291,
18740-18752.
[DOI no: ]
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PubMed id
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Abstract
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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.
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