The Structural Basis of Ligand Recognition by Natural Killer Cell Receptors

Figure 5

Structures of NKp46 homologous proteins ((a), (b)) FcαRI, ((c), (d)) KIR2DL2, ((e), (f)) ILT2, and ((g), (h)) GP VI shown in cartoon representation with transparent surface also shown. The known ligand binding residues of these molecules are given in ball and stick representation with the surface of these amino acids also highlighted. KIR binding to MHC molecules utilizes a number of residues found in the AB, CC′, EF loop regions of D1, the GA hinge region between D1 and D2, and the BC loop and FG loop regions of D2. ILT-2 uses residues located in the C strand, the CE loop region, EF loop region, and G strand of D1 while also using residues located in the BC loop region of D2. GP VI utilizes residues in the CC′ loop, C strand, CE loop, E strand, EF loop, and F strand of D1 while also using the FG loop region of D2. CD89 uses residues from the BC loop, C′ strand, C′E loop, and the FG loop of D1 in a side-on mechanism of binding in contrast to the other homologous proteins which all utilize the membrane distal face of the receptor for ligand binding. The lower panel shows the respective molecules in an “above-cell view” orientation which also highlights their ligand binding sites.