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Review
. 2015 Dec 3;7(12):5268-75.
doi: 10.3390/toxins7124880.

Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin

Masataka Oda  1 , Yutaka Terao  2 , Jun Sakurai  3 , Masahiro Nagahama  4
Affiliations
Review

Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin

Masataka Oda et al. Toxins (Basel). .

Abstract

Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1-250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251-370 aa, C-domain), which is the membrane-binding site. Immunization of mice with the C-domain of alpha-toxin prevents the gas gangrene caused by C. perfringens, whereas immunization with the N-domain has no effect. The central loop domain (55-93 aa), especially H….SW(84)Y(85)….G, plays an important role in the interaction with ganglioside GM1a. The toxin binds to lipid rafts in the presence of a GM1a/TrkA complex, and metabolites from phosphatidylcholine to diacylglycerol through the enzymatic activity of alpha-toxin itself. These membrane dynamics leads to the activation of endogenous PLCγ-1 via TrkA. In addition, treatment with alpha-toxin leads to the formation of diacylglycerol at membrane rafts in ganglioside-deficient DonQ cells; this in turn triggers endocytosis and cell death. This article summarizes the current the membrane-binding mechanism of alpha-toxin in detail.

Keywords: C-domain; Clostridium perfringens; TrkA; alpha-toxin; central loop domain; endocytosis; ganglioside GM1a; phospholipid; vaccine.

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Figures

Figure 1
Figure 1
Three domains of Clostridium perfringens alpha-toxin.
Figure 2
Figure 2
Model of alpha-toxin-induced signal transduction via GM1a/TrkA.
Figure 3
Figure 3
Model of alpha-toxin-induced endocytosis.
See this image and copyright information in PMC

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