Characterization of -Glucan Recognition Site on C-Type Lectin, Dectin 1
نویسندگان
چکیده
Dectin 1 is a mammalian cell surface receptor for (133)-D-glucans. Since (133)-D-glucans are commonly present on fungal cell walls, it has been suggested that dectin 1 is important for recognizing fungal invasion. In this study we tried to deduce the amino acid residues in dectin 1 responsible for -glucan recognition. HEK293 cells transfected with mouse dectin 1 cDNA could bind to a gel-forming (133)-Dglucan, schizophyllan (SPG). The binding of SPG to a dectin 1 transfectant was inhibited by pretreatment with other -glucans having a (133)-D-glucosyl linkage but not by pretreatment with -glucans. Dectin 1 has a carbohydrate recognition domain (CRD) consisting of six cysteine residues that are highly conserved in C-type lectins. We prepared 32 point mutants with mutations in the CRD and analyzed their binding to SPG. Mutations at Trp and His resulted in decreased binding to -glucan. Monoclonal antibody 4B2, a dectin1 monoclonal antibody which had a blocking effect on the -glucan interaction, completely failed to bind the dectin-1 mutant W221A. A mutant with mutations in Trp and His did not have a collaborative effect on Toll-like receptor 2-mediated cellular activation in response to zymosan. These amino acid residues are distinct from residues in other sugar-recognizing peptide sequences of typical C-type lectins. These results suggest that the amino acid sequence W221-I222-H223 is critical for formation of a -glucan binding site in the CRD of dectin 1.
منابع مشابه
Biol. Pharm. Bull. 29(8) 1580—1586 (2006)
expressed on murine macrophages, dendritic cells, and neutrophils. Murine Dectin-1 (mDectin-1) is involved in the recognition of b-glucan, which is the main component of the fungal cell wall, and induces phagocytosis, the generation of reactive oxygen, and the production of proinflammatory cytokines. Thus, it has become clear that various murine anti-fungal immune responses are mediated by Dect...
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