A synthetic peptidoglycan fragment as a competitive inhibitor of the melanization cascade

Won Park Ji, Byung Rok Je, Shunfu Piao, Seiichi Inamura, Yukari Fujimoto, Koichi Fukase, Shoichi Kusumoto, Kenneth Söderhäll, Nam Chul Ha, Bok Luel Lee

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Abstract

Melanin synthesis is essential for defense and development but must be tightly controlled because systemic hyperactivation of the prophenoloxidase and excessive melanin synthesis are deleterious to the hosts. The melanization cascade of the arthropods can be activated by bacterial lysine-peptidoglycan (PGN), diaminopimelic acid (DAP)-PGN, or fungal β-1,3-glucan. The molecular mechanism of how DAP- or Lys-PGN induces melanin synthesis and which molecules are involved in distinguishing these PGNs are not known. The identification of PGN derivatives that can work as inhibitors of the melanization cascade and the characterization of PGN recognition molecules will provide important information to clarify how the melanization is regulated and controlled. Here, we report that a novel synthetic Lys-PGN fragment ((GlcNAc-Mur-NAc-L-Ala-D-isoGln-L-Lys-D- Ala)2, T-4P2) functions as a competitive inhibitor of the natural PGN-induced melanization reaction. By using a T-4P2-coupled column, we purified the Tenebrio molitor PGN recognition protein (Tm-PGRP) without causing activation of the prophenoloxidase. The purified Tm-PGRP recognized both Lys- and DAP-PGN. In vitro reconstitution experiments showed that Tm-PGRP functions as a common recognition molecule of Lys- and DAP-PGN-dependent melanization cascades.

Original languageEnglish
Pages (from-to)7747-7755
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number12
DOIs
Publication statusPublished - 2006 Mar 24

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ji, W. P., Je, B. R., Piao, S., Inamura, S., Fujimoto, Y., Fukase, K., Kusumoto, S., Söderhäll, K., Ha, N. C., & Lee, B. L. (2006). A synthetic peptidoglycan fragment as a competitive inhibitor of the melanization cascade. Journal of Biological Chemistry, 281(12), 7747-7755. https://doi.org/10.1074/jbc.M510058200