Figure 8.

Interaction of Ly49 receptors with MHC-I in trans and cis. (A) Trans interaction of an Ly49 receptor with two MHC-I molecules, based on the structures of Ly49L (3G8L) and the Ly49C–H-2K^b complex (3C8K). The α1, α2, and α3 domains of the MHC-I heavy chain are cyan; β₂m is green; Ly49 NKD is red; helix α3_S of the Ly49 stalk and loop L_S connecting α3_S to the NKD are blue; the disulfide bond linking the α3_S helices is magenta. The predicted α1_S and α2_S helices of the stalk are orange and yellow, respectively, with the disulfide bond in magenta. The Ly49 homodimer on the NK cell binds two MHC-I molecules on the target cell. To bind in trans, the stalks must adopt a backfolded conformation, as the N-termini of the Ly49 monomers point away from the NK cell membrane (Ly49s are type II transmembrane proteins). (B) Cis interaction of Ly49 with MHC-I, based on the structure of Ly49L and the Ly49A–H-2D^d complex (1QO3). The L_S loops connecting the α3_S helices to the NKDs are drawn arbitrarily. The Ly49 homodimer binds one MHC-I molecule on the NK cell itself. In this case, the stalks must assume an extended conformation, as the N-termini of the Ly49 monomers point toward the NK cell. Reproduced with permission from Immunity (106).