NKR-P1A protein, an activating receptor of rat natural killer cells, binds to the chitobiose core of uncompletely glycosylated N-linked glycans, and to linear chitooligomers.
NKR-P1 represent a family of activating receptors in rodent natural killer cells related to C-type animal lectins. We identify here the elements involved in the reactivity of the major receptor of rat, NKR-P1A, with N-linked oligosaccharides of glycoproteins. Plate inhibition assays with isolated, structurally defined N-glycans as inhibitors of binding of NKR-P1A to GlcNAc16-BSA revealed that the removal of both the external sialic acids and the penultimate galactose residues resulted in attaining of significant inhibitory activities. Surprisingly, additional plate inhibition and glycoprotein overlay experiments brought evidence that the core chitobiose, depending on its substitution, can per se support the interaction with NKR-P1A. In a series of linear chitooligomers (n = 2-7), the inhibitory activities reached a maximum for the chitotetraose. The ability of NKR-P1 to recognize both the periphery and the core region of complex type oligosaccharides may define its dual specificity towards carbohydrate components of eukaryotic (e.g., tumor) cell surfaces, but also reflect an evolutionarily conserved reactivity with microbial saccharides important in immune recognition and signaling functions.
Bezouska
K
K
Department of Biochemistry, Faculty of Science, Charles University Prague, Czech Republic.
Sklenár
J
J
Dvoráková
J
J
Havlícek
V
V
Pospísil
M
M
Thiem
J
J
Kren
V
V
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D002236:Carbohydrate Conformation; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009844:Oligosaccharides / Q000378:metabolism; D010047:Ovalbumin / Q000378:metabolism; D010059:Ovomucin / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*
D000954:Antigens, Surface; D004187:Disaccharides; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009844:Oligosaccharides; D011134:Polysaccharides; D011971:Receptors, Immunologic; D010059:Ovomucin; C032438:chitobiose; D010047:Ovalbumin; D019158:N-Acetylneuraminic Acid