Abstract

Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

Highlights

  • Clostridial binary toxins are ADP-ribosylating toxins that utilize globular actin as a substrate and depolymerize filamentous actin capped by ADP-ribosylated actin in sensitive cells

  • Ib is delivered to lysosomes for degradation, and degraded Ib is exposed on the cell part (Ib-sensitive cells): Ib oligomerizes mainly in non-lipid rafts in the plasma membranes and is not surface

  • These toxins possess the potency toIota-toxin internalizeand intoC2 cells andbelong to release into theThese cytoplasmic

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Summary

Introduction

Clostridial binary toxins are ADP-ribosylating toxins that utilize globular actin as a substrate and depolymerize filamentous actin capped by ADP-ribosylated actin in sensitive cells. The amino acid sequences of the former three binding components are more similar to each other than to C2II. These clostridial binary toxins consist of two separate protein components: the enzymatic. The binding components Ib and C2II (B components of iota-toxin and C2 toxin, respectively) recognize different cellular receptors and are implicated in the uptake of A components into the intracellular space [3,8,9,10,11]. The A component (Ia) of iota-toxin mono-ADP-ribosylates non-muscle and muscle G-actin at arginine-177. Iota-toxin produced by C. perfringens type E consists of two components, an enzymatic component (Ia) and a binding component (Ib) [2,3,10,11]. Iota-toxin is considered to be a key virulence factor of intestinal pathogenesis

Structure of Ia and Ib
Binding and Internalization of Iota-Toxin
Intracellular
Translocation of Ia across the Endosomal Membrane
Cytotoxicity of Ib
Structure of C2I and C2II
Binding and Internalization of C2 Toxin
Initialstep stepin in the the internalization
Intracellular Trafficking of C2 Toxin
Findings
Conclusions
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