The mechanism of membrane insertion for a cholesterol-dependent cytolysin: A novel paradigm for pore-forming toxins

Oleg Shatursky, Alejandro P. Heuck, Laura A. Shepard, Jamie Rossjohn, Michael W. Parker, Arthur E. Johnson, Rodney K. Tweten

Research output: Contribution to journalArticleResearchpeer-review

293 Citations (Scopus)

Abstract

Perfringolysin O (PFO), a water-soluble monomeric cytolysin secreted by pathogenic Clostridium perfringens, oligomerizes and forms large pores upon encountering cholesterol-containing membranes. Whereas all pore-forming bacterial toxins examined previously have been shown to penetrate the membrane using a single amphipathic β hairpin per polypeptide, cysteine- scanning mutagenesis and multiple independent fluorescence techniques here reveal that each PFO monomer contains a second domain involved in pore formation, and that each of the two amphipathic β hairpins completely spans the membrane. In the soluble monomer, these transmembrane segments are folded into six α helices. The insertion of two transmembrane hairpins per toxin monomer and the major change in secondary structure are striking and define a novel paradigm for the mechanism of membrane insertion by a cytolytic toxin.

Original languageEnglish
Pages (from-to)293-299
Number of pages7
JournalCell
Volume99
Issue number3
DOIs
Publication statusPublished - 29 Oct 1999
Externally publishedYes

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