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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10850-10861
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number17
DOIs
Publication statusPublished - Apr 24 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A pore-forming toxin requires a specific residue for its activity in membranes with particular physicochemical properties'. Together they form a unique fingerprint.

Cite this