The N-terminal Arg residue is essential for autocatalytic activation of a lipopolysaccharide-responsive protease zymogen

Yuki Kobayashi, Takafumi Shiga, Toshio Shibata, Miyuki Sako, Katsumi Maenaka, Takumi Koshiba, Hikaru Mizumura, Toshio Oda, Shun Ichiro Kawabata

研究成果: ジャーナルへの寄稿学術誌査読

12 被引用数 (Scopus)

抄録

Factor C, a serine protease zymogen involved in innate immune responses in horseshoe crabs, is known to be autocatalytically activated on the surface of bacterial lipopolysaccharides, but the molecular mechanism of this activation remains unknown. In this study, we show that wild-type factor C expressed in HEK293S cells exhibits a lipopolysaccharide-induced activity equivalent to that of native factor C. Analysis of the N-terminal addition, deletion, or substitution mutants shows that the N-terminal Arg residue and the distance between the N terminus and the tripartite of lipopolysaccharide-binding site are essential factors for autocatalytic activation, and that the positive charge of theNterminus may interact with an acidic amino acid(s) of the molecule to convert the zymogen into an active form. Chemical cross-linking experiments indicate that the N terminus is required to form a complex of the factor C molecules in a sufficiently close vicinity to be chemically cross-linked on the surface of lipopolysaccharides. We propose a molecular mechanism of the autocatalytic activation of the protease zymogen on lipopolysaccharides functioning as a platform to induce specific protein-protein interaction between the factor C molecules.

本文言語英語
ページ(範囲)25987-25995
ページ数9
ジャーナルJournal of Biological Chemistry
289
37
DOI
出版ステータス出版済み - 9月 12 2014

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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