PDBsum entry 1p6f

Immune system

PDB id: 1p6f

Contents

Protein chain

188 a.a. *

Waters ×86

* Residue conservation analysis

PDB id:

1p6f

Name:

Immune system

Title:

Structure of the human natural cytotoxicity receptor nkp46

Structure:

Natural cytotoxicity triggering receptor 1. Chain: a. Fragment: extracellular d1 and d2 domains. Synonym: nkp46. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.207 R-free: 0.251

Authors:

C.E.Foster,M.Colonna,P.D.Sun

Key ref:

C.E.Foster et al. (2003). Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors. J Biol Chem, 278, 46081-46086. PubMed id: 12960161 DOI: 10.1074/jbc.M308491200

Date:

29-Apr-03 Release date: 09-Dec-03

Protein chain

O76036  (NCTR1_HUMAN) -  Natural cytotoxicity triggering receptor 1 from Homo sapiens

Seq: 304 a.a.

Struc: 188 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1074/jbc.M308491200

J Biol Chem 278:46081-46086 (2003)

PubMed id: 12960161

Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors.

C.E.Foster, M.Colonna, P.D.Sun.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 46081-46086) copyright 2003.

Figures were selected by an automated process.