Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.
"They consist of a light chain (L, 50 kDa) and a heavy chain (H, 100 kDa) linked by a strictly conserved interchain disulfide bond. Figure 1 shows the crystal structures of BoNT/A1 and of BoNT/E1; BoNT/B1 is very similar to BoNT/A1 (not shown)   . They consist of four domains: HC-C (25 kDa, in green in figure 1) involved in nerve terminal binding; HC-N (25 kDa purple in figure 1) of unknown function, though there is evidence that it binds to membrane lipids  ; L (red in fig. "
Biochimica et Biophysica Acta 08/2015; DOI:10.1016/j.bbamem.2015.08.014 · 4.66 Impact Factor
"Under trade names including Botox Cosmetics (USA), Vistabel (Europe), Azzalure, and Bocouture, BoNT/A is in popular use for cosmetic applications (Evidente and Adler, 2010; Markey, 2000). All BoNTs comprise a protease domain (LC), a translocation domain (H N ) and a receptor-binding domain (H C ) (Montal, 2010; Rossetto et al., 2014; Swaminathan, 2011), but there can be differences in the structural organization of the domains, as was shown for example for serotype E (Kumaran et al., 2009). In the maturation process of the toxin, the original single polypeptide chain is proteolytically cleaved into two parts. "
"Despite of existence of a high number of isoforms, all BoNTs are structurally similar and consist of two chains linked by a unique disulphide bond: a light chain (L, 50 kDa) and a heavy chain (H, 100 kDa). The complete crystallographic structures of three BoNTs (A1, B1 and E1) (Lacy et al., 1998; Swaminathan and Eswaramoorthy, 2000; Kumaran et al., 2009; Montal, 2010) reveal different domains, which are functionally linked to the four steps of the mechanism of neuron intoxication by BoNTs. 1) Binding: the C-terminal domain of the heavy chain (HC) is responsible for the neurospecific binding. Notwithstanding the major effort of many different laboratories in the world, the receptors of BoNT/C (and many toxin subtypes) have not been yet identified. "
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