Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form

Jamie Rossjohn, Susanne C. Feil, William J. McKinstry, Rodney K. Tweten, Michael W. Parker

Research output: Contribution to journalArticleResearchpeer-review

383 Citations (Scopus)

Abstract

The mechanisms by which proteins gain entry into membranes is a fundamental problem in biology. Here, we present the first crystal structure of a thiol-activated cytolysin, perfringolysin O, a member of a large family of toxins that kill eukaryotic cells by punching holes in their membranes. The molecule adopts an unusually elongated shape rich in β sheet. We have used electron microscopy data to construct a detailed model of the membrane channel form of the toxin. The structures reveal a novel mechanism for membrane insertion. Surprisingly, the toxin receptor, cholesterol, appears to play multiple roles: targeting, promotion of oligomerization, triggering a membrane insertion competent form, and stabilizing the membrane pore.

Original languageEnglish
Pages (from-to)685-692
Number of pages8
JournalCell
Volume89
Issue number5
DOIs
Publication statusPublished - 30 May 1997
Externally publishedYes

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