NDLI: Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lewis, Richard J. Mickiewicz, Katarzyna M. Brooks, Colin G. Gays, Frances
Description	Country affiliation: United kingdom Author Affiliation: Mickiewicz KM ( Institute of Cell and Molecular Biosciences, University of Newcastle, Newcastle NE2 4HH, United Kingdom.)
Abstract	Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. These residues are highly conserved in the Ly49 family. Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Histocompatibility Antigens Class I Metabolism Nk Cell Lectin-like Receptor Subfamily A Genetics Amino Acid Sequence Animals Binding Sites Immunology Cell Line Evolution, Molecular Genetic Variation Killer Cells, Natural Mice Mice, Inbred Balb C Mice, Inbred C57bl Models, Molecular Mutagenesis, Site-directed Protein Binding Protein Isoforms Sequence Alignment Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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