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MACPF/CDC Proteins - Agents of Defence, Attack and Invasion pp 63–81Cite as

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

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Part of the book series: Subcellular Biochemistry ((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.

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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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  1. Department of Biochemistry and Molecular Biology, University of Massachusetts, 710 N. Pleasant St., Lederle GRT, Amherst, MA, 01003, USA

    Benjamin B. Johnson & Alejandro P. Heuck

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Correspondence to Alejandro P. Heuck .

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  1. National Institute of Chemistry, Ljubljana, Slovenia, Laboratory for Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia

    Gregor Anderluh

  2. Division of Structural Biology, University of Oxford Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

    Robert Gilbert

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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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