Binding of the natural killer cell inhibitory receptor Ly49A to its major histocompatibility complex class I ligand. Crucial contacts include both H-2Dd AND beta 2-microglobulin.

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TitleBinding of the natural killer cell inhibitory receptor Ly49A to its major histocompatibility complex class I ligand. Crucial contacts include both H-2Dd AND beta 2-microglobulin.
Publication TypeJournal Article
Year of Publication2002
AuthorsWang, J, Whitman, MC, Natarajan, K, Tormo, J, Mariuzza, RA, Margulies, DH
JournalJ Biol Chem
Volume277
Issue2
Pagination1433-42
Date Published2002 Jan 11
ISSN0021-9258
KeywordsAmino Acid Sequence, Animals, Antibodies, Monoclonal, Antigens, Ly, Antigens, Surface, beta 2-Microglobulin, Binding Sites, Carrier Proteins, Dimerization, H-2 Antigens, Killer Cells, Natural, Lectins, C-Type, Ligands, Major Histocompatibility Complex, Membrane Proteins, Mice, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, NK Cell Lectin-Like Receptor Subfamily A, Protein Binding, Protein Structure, Quaternary, Receptors, Immunologic, Receptors, NK Cell Lectin-Like, Recombinant Proteins, Surface Plasmon Resonance
Abstract

Ly49A, an inhibitory C-type lectin-like mouse natural killer cell receptor, functions through interaction with the major histocompatibility complex class I molecule, H-2D(d). The x-ray crystal structure of the Ly49A.H-2D(d) complex revealed that homodimeric Ly49A interacts at two distinct sites of H-2D(d): Site 1, spanning one side of the alpha1 and alpha2 helices, and Site 2, involving the alpha1, alpha2, alpha3, and beta(2)m domains. Mutants of Ly49A, H-2D(d), and beta(2)-microglobulin at intermolecular contacts and the Ly49A dimer interface were examined for binding affinity and kinetics. Although mutations at Site 1 had little affect, several at Site 2 and at the dimer interface hampered the Ly49A.H-2D(d) interaction, with no effect on gross structure or T cell receptor interaction. The region surrounding the most critical residues (in H-2D(d), Asp(122); in Ly49A, Asp(229), Ser(236), Thr(238), Arg(239), and Asp(241); and in beta(2)-microglobulin, Gln(29) and Lys(58)) of the Ly49A.H-2D(d) interface at Site 2 includes a network of water molecules, suggesting a molecular basis for allelic specificity in natural killer cell recognition.

DOI10.1074/jbc.M110316200
Alternate JournalJ. Biol. Chem.
PubMed ID11696552
Grant ListAI47900 / AI / NIAID NIH HHS / United States
GM52801 / GM / NIGMS NIH HHS / United States