A pore-forming toxin requires a specific residue for its activity in membranes with particular physicochemical properties

Koldo Morante, Jose M.M. Caaveiro, Koji Tanaka, Juan Manuel González-Mañas, Kouhei Tsumoto

研究成果: Contribution to journalArticle査読

29 被引用数 (Scopus)

抄録

The physicochemical landscape of the bilayer modulates membrane protein function. Actinoporins are a family of potent hemolytic proteins from sea anemones acting at the membrane level. This family of cytolysins preferentially binds to target membranes containing sphingomyelin, where they form lytic pores giving rise to cell death. Although the cytolytic activity of the actinoporin fragaceatoxin C (FraC) is sensitive to vesicles made of various lipid compositions, it is far from clear how this toxin adjusts its mechanism of action to a broad range of physiochemical landscapes. Herein, we show that the conserved residue Phe-16 of FraC is critical for pore formation in cholesterolrich membranes such as those of red blood cells. The interaction of a panel of muteins of Phe-16 with model membranes composed of raft-like lipid domains is inactivated in cholesterol-rich membranes but not in cholesterol-depleted membranes. These results indicate that actinoporins recognize different membrane environments, resulting in a wider repertoire of susceptible target membranes (and preys) for sea anemones. In addition, this study has unveiled promising candidates for the development of protein-based biosensors highly sensitive to the concentration of cholesterol within the membrane.

本文言語英語
ページ(範囲)10850-10861
ページ数12
ジャーナルJournal of Biological Chemistry
290
17
DOI
出版ステータス出版済み - 4 24 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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