Crystal structure of the Ly49I natural killer cell receptor reveals variability in dimerization mode within the Ly49 family.

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TitleCrystal structure of the Ly49I natural killer cell receptor reveals variability in dimerization mode within the Ly49 family.
Publication TypeJournal Article
Year of Publication2002
AuthorsDimasi, N, Sawicki, MW, Reineck, LA, Li, Y, Natarajan, K, Margulies, DH, Mariuzza, RA
JournalJ Mol Biol
Date Published2002 Jul 12
KeywordsAmino Acid Sequence, Animals, Antigens, Ly, Base Sequence, Binding Sites, Crystallography, X-Ray, Dimerization, DNA, Genetic Variation, Histocompatibility Antigens Class I, Killer Cells, Natural, Lectins, C-Type, Ligands, Membrane Glycoproteins, Mice, Models, Molecular, Molecular Sequence Data, NK Cell Lectin-Like Receptor Subfamily A, NK Cell Lectin-Like Receptor Subfamily K, Protein Structure, Quaternary, Receptors, Immunologic, Receptors, Natural Killer Cell, Receptors, NK Cell Lectin-Like, Sequence Homology, Amino Acid

Natural killer (NK) cells play a crucial role in the detection and destruction of virally infected and tumor cells during innate immune responses. The cytolytic activity of NK cells is regulated through a balance of inhibitory and stimulatory signals delivered by NK receptors that recognize classical major histocompatabilty complex class I (MHC-I) molecules, or MHC-I homologs such as MICA, on target cells. The Ly49 family of NK receptors (Ly49A through W), which includes both inhibitory and activating receptors, are homodimeric type II transmembrane glycoproteins, with each subunit composed of a C-type lectin-like domain tethered to the membrane by a stalk region. We have determined the crystal structure, at 3.0 A resolution, of the murine inhibitory NK receptor Ly49I. The Ly49I monomer adopts a fold similar to that of other C-type lectin-like NK receptors, including Ly49A, NKG2D and CD69. However, the Ly49I monomers associate in a manner distinct from that of these other NK receptors, forming a more open dimer. As a result, the putative MHC-binding surfaces of the Ly49I dimer are spatially more distant than the corresponding surfaces of Ly49A or NKG2D. These structural differences probably reflect the fundamentally different ways in which Ly49 and NKG2D receptors recognize their respective ligands: whereas the single MICA binding site of NKG2D is formed by the precise juxtaposition of two monomers, each Ly49 monomer contains an independent binding site for MHC-I. Hence, the structural constraints on dimerization geometry may be relatively relaxed within the Ly49 family. Such variability may enable certain Ly49 receptors, like Ly49I, to bind MHC-I molecules bivalently, thereby stabilizing receptor-ligand interactions and enhancing signal transmission to the NK cell.

Alternate JournalJ. Mol. Biol.
PubMed ID12096910
Grant ListAI36900 / AI / NIAID NIH HHS / United States
AI47900 / AI / NIAID NIH HHS / United States