|Title||Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b).|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Dam, J, Guan, R, Natarajan, K, Dimasi, N, Chlewicki, LK, Kranz, DM, Schuck, P, Margulies, DH, Mariuzza, RA|
|Date Published||2003 Dec|
|Keywords||Animals, Antigens, Ly, Crystallography, X-Ray, Dimerization, H-2 Antigens, Killer Cells, Natural, Lectins, C-Type, Major Histocompatibility Complex, NK Cell Lectin-Like Receptor Subfamily A, Protein Binding, Protein Structure, Quaternary, Receptors, NK Cell Lectin-Like, Substrate Specificity|
The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.
|Alternate Journal||Nat. Immunol.|