Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes

Abstract

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among different serotypes of C. botulinum. The results indicate that neurotoxins type A, C, D, E and F contain a coiled-coil domain while types B and type G neurotoxin do not. Interestingly, phylogenetic analysis based on neurotoxin sequences has further confirmed that serotypes B and G are closely related. These results suggest that neurotoxin has multi-domain structure, and coiled-coil domain plays an important role in oligomerisation of the neurotoxin. Domain analysis may help to identify effective antibodies to treat Botulinum toxin intoxication.

Update on Non-Interchangeability of Botulinum Neurotoxin Products

“…Some serotypes do not have the HA genes (BoNT/E and/F) and may only form the M-PTC [ 32 ]. The NAPs play various roles in BoNT’s activity, including protecting the neurotoxin from degradation [ 42 ] and potentially reducing exposure to the immune system [ 43 ]. Additional actions of the NAPs are described in a subsequent section (Role of NAPs in the Pharmacodynamic Action of BoNTs).…”

“…BoNT/A is naturally expressed in Clostridium botulinum as PTCs, with the complex conferring a thermodynamically stable structure [ 62 ] that protects the 150 kDa neurotoxin in harsh environments [ 63 , 64 ]. The NAPs have been shown to protect BoNT from proteolysis [ 42 ] and alter the secondary structure of neurotoxin conformation [ 62 ].…”

Clinical applications of amylase: Novel perspectives

“…41 Interestingly, organisms in this genus are capable of prolific amylase secretion, and may consequently increase amylase levels around the infected site by several orders of magnitude. [41][42][43][44][45][46][47] Several organisms in these genuses are responsible for life-threatening human infection, often requiring urgent treatment including C. perfringens (gas gangrene), 48 C. tetanii (tetanus), 49 C. difficile (hospital acquired pseudomembranous colitis), 50,51 and B. cereus (food poisoning). Several Bacillus species are exploited in the alimentary biotechnology industry for their prolific amylase production.…”

The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins

“…These bacterial neurotoxins (molecular weight ~150 kDa) have four domains that comprise their three-dimensional (3D) structures ( Figure 1 ) [ 11 , 12 , 13 , 14 , 15 ]. BoNT/A was the first holotoxin serotype to be resolved crystallographically [ 17 ] (PDB ID: 3BTA).…”