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PDBsum entry 1p6f
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Immune system
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PDB id
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1p6f
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the human natural killer (nk) cell activating receptor nkp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors.
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Authors
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C.E.Foster,
M.Colonna,
P.D.Sun.
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Ref.
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J Biol Chem, 2003,
278,
46081-46086.
[DOI no: ]
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PubMed id
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Abstract
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Natural cytotoxicity receptors (NCR) mediate lysis of a variety of tumor and
virus-infected cells by natural killer (NK) cells. Upon engagement, NCR trigger
the cytolytic activity and cytokine release of NK cells through association with
ITAM-containing signaling molecules. To further understand the function of these
receptors in activation of natural cytotoxicity, we determined the crystal
structure of the extracellular ligand binding domain of human NKp46, one of
three known NCR, at 2.2-A resolution. The overall fold and disposition of the
two C2-set immunoglobulin domains are similar to the D1D2 domains of inhibitory
killer cell Ig-like receptor (KIR) and Ig-like transcript (ILT) receptors. As
the cellular ligands of NKp46 have not yet been defined, the known ligand
binding sites of KIR and ILT were compared with the corresponding structural
regions of NKp46 in an effort to identify potential areas suitable for molecular
recognition. A potential binding site for influenza hemagglutinin is located
near the interdomain hinge, a region that mediates ligand binding in KIR. The
structural similarity of NKp46 to inhibitory KIR receptors may have implications
for how NK cells balance activating and inhibitory signals.
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Figure 2.
FIG. 2. Comparison of NKp46 to other Ig-like receptors. The
structure of NKp46 (black) is superimposed with that of KIR2DL2
(red) in A, with ILT2 (green) in B, and with Fc  RI
(aqua) in C.
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Figure 4.
FIG. 4. Ligand binding sites of leukocyte receptor complex
immunoreceptors. A, the structure of KIR2DL2 (Protein Data Bank
entry 1efx [PDB]
) with residues contacting HLA-Cw3 displayed as ball-and-stick
models in gray (41). B, ILT2 (1g0x [PDB]
) with residues implicated in binding to UL18 (37, 51). C, Fc
RI
(10W0) with residues contacting Fc displayed. D, the
structure of NKp46 with putative ligand binding residues
displayed. Residues in red correspond to the KIR binding site;
those in aqua and green correspond to the Fc RI and ILT2 binding
sites, respectively. The location of the potentially
glycosylated residue Thr104 is shown.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
46081-46086)
copyright 2003.
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