Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands

TitleSymmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands
Publication TypeJournal Article
Year of Publication2003
AuthorsMcFarland, B. J., Kortemme T., Yu S. F., Baker D., & Strong R. K.
JournalStructure
Volume11
Issue4
Pagination411-22
Date Published2003 Apr
ISSN0969-2126
KeywordsAmino Acids, Animals, Collaborative Publication, Crystallography, X-Ray, Genes, MHC Class I, HLA-A Antigens, Humans, Ligands, Mice, Models, Molecular, Mutagenesis, NK Cell Lectin-Like Receptor Subfamily K, Protein Structure, Tertiary, Receptors, Immunologic, Receptors, Natural Killer Cell
Abstract

Engagement of diverse protein ligands (MIC-A/B, ULBP, Rae-1, or H60) by NKG2D immunoreceptors mediates elimination of tumorigenic or virally infected cells by natural killer and T cells. Three previous NKG2D-ligand complex structures show the homodimeric receptor interacting with the monomeric ligands in similar 2:1 complexes, with an equivalent surface on each NKG2D monomer binding intimately to a total of six distinct ligand surfaces. Here, the crystal structure of free human NKG2D and in silico and in vitro alanine-scanning mutagenesis analyses of the complex interfaces indicate that NKG2D recognition degeneracy is not explained by a classical induced-fit mechanism. Rather, the divergent ligands appear to utilize different strategies to interact with structurally conserved elements of the consensus NKG2D binding site.

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