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Perfringolysin O Structure and Mechanism of Pore Formation as a Paradigm for Cholesterol-Dependent Cytolysins

  • Benjamin B. Johnson
  • Alejandro P. HeuckEmail author
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 80)

Abstract

Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores by inserting a large β-barrel into cholesterol-containing membrane bilayers. Binding of water-soluble CDCs to the membrane triggers the formation of oligomers containing 35–50 monomers. The coordinated insertion of more than seventy β-hairpins into the membrane requires multiple structural conformational changes. Perfringolysin O (PFO), secreted by Clostridium perfringens, has become the prototype for the CDCs. In this chapter, we will describe current knowledge on the mechanism of PFO cytolysis, with special focus on cholesterol recognition, oligomerization, and the conformational changes involved in pore formation.

Keywords

β-barrel Cholesterol Cholesterol-dependent cytolysins Lysteriolysin O Membrane Perfringolysin O Pneumolysin Pore formation Streptolysin O Toxin 

Abbreviations

CDCs

Cholesterol-dependent cytolysins

D1, D2, D3, and D4

Domain 1, domain 2, domain 3, and domain 4

L1, L2, and L3

Loop 1, loop 2, and loop 3

PFO

Perfringolysin O

TMH1 and TMH2

Transmembrane hairpin 1 and transmembrane hairpin 2

Notes

Acknowledgments

Work in the author’s laboratory was supported by Grant Number GM 097414 from the National Institute of Health (A.P.H). B.B.J. was partially supported by the National Science Foundation, Integrative Graduate Education and Research Traineeship (IGERT), Institute for Cellular Engineering (DGE-0654128).

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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of MassachusettsAmherstUSA

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