Nature Immunology
4, 1213 - 1222 (2003)
Published online: 2 November 2003; | doi:10.1038/ni1006
Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2KbJulie Dam1, 6, Rongjin Guan1, 6, Kannan Natarajan2, 6, Nazzareno Dimasi1, 5, 6, Lukasz K Chlewicki3, David M Kranz3, Peter Schuck4, David H Margulies2
& Roy A Mariuzza11
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. 2
Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. 3
Department of Biochemistry, University of Illinois, Urbana, Ilinois 61801, USA. 4
Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, Maryland 20892, USA. 5
Present address: Istituto Giannina Gaslini, Largo Gerolamo Gaslini 5, 16147 Genova, Italy. 6
These authors contributed equally to this work.
Correspondence should be addressed to David H Margulies dhm@nih.gov or Roy A Mariuzza mariuzza@carb.nist.govThe 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-2Kb. 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.
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