Characterization of β-Glucan Recognition Site on C-Type Lectin, Dectin 1

• Yoshiyuki Adachi

  Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji

• Takashi Ishii

  Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji

• Yoshihiko Ikeda

  Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji

• Akiyoshi Hoshino

  Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji

• Hiroshi Tamura

  Seikagaku Corporation, Higashiyamato, Tokyo, Japan

• Jun Aketagawa

  Seikagaku Corporation, Higashiyamato, Tokyo, Japan

• Shigenori Tanaka

  Seikagaku Corporation, Higashiyamato, Tokyo, Japan

• Naohito Ohno

  Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji

抄録

Dectin 1 is a mammalian cell surface receptor for (1→3)-β- d -glucans. Since (1→3)-β- 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 β-glucan recognition. HEK293 cells transfected with mouse dectin 1 cDNA could bind to a gel-forming (1→3)-β- d -glucan, schizophyllan (SPG). The binding of SPG to a dectin 1 transfectant was inhibited by pretreatment with other β-glucans having a (1→3)-β- d -glucosyl linkage but not by pretreatment with α-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 221 and His 223 resulted in decreased binding to β-glucan. Monoclonal antibody 4B2, a dectin- 1 monoclonal antibody which had a blocking effect on the β-glucan interaction, completely failed to bind the dectin-1 mutant W221A. A mutant with mutations in Trp 221 and His 223 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 β-glucan binding site in the CRD of dectin 1.

収録刊行物

• Infection and Immunity

  Infection and Immunity 72 (7), 4159-4171, 2004-07

  American Society for Microbiology

キーワード

• Infectious Diseases
• Immunology
• Microbiology
• Parasitology

詳細情報

• CRID: 1361699995480660864
• NII論文ID: 30020832489
• DOI: 10.1128/iai.72.7.4159-4171.2004
• ISSN: 10985522
• ISSN: 00199567
• ISSN: http://id.crossref.org/issn/00199567
• Web Site: https://journals.asm.org/doi/pdf/10.1128/IAI.72.7.4159-4171.2004
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