Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b).
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.
Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA.
Julie
J
Dam
Rongjin
R
Guan
Kannan
K
Natarajan
Nazzareno
N
Dimasi
Lukasz K
LK
Chlewicki
David M
DM
Kranz
Peter
P
Schuck
David H
DH
Margulies
Roy A
RA
Mariuzza
D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D019281:Dimerization; D006183:H-2 Antigens / Q000737:chemistry* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008285:Major Histocompatibility Complex / Q000502:physiology; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011485:Protein Binding / Q000276:immunology; D020836:Protein Structure, Quaternary; D055630:Receptors, NK Cell Lectin-Like; D013379:Substrate Specificity / Q000502:physiology
D000950:Antigens, Ly; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C527088:Klra1 protein, mouse; C527091:Klra3 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like