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.
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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
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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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Johnson, B.B., Heuck, A.P. (2014). Perfringolysin O Structure and Mechanism of Pore Formation as a Paradigm for Cholesterol-Dependent Cytolysins. In: Anderluh, G., Gilbert, R. (eds) MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Subcellular Biochemistry, vol 80. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8881-6_5
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