Structural highlights
Function
[BXA1_CLOBO] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.
Publication Abstract from PubMed
The binding specificity of botulinum neurotoxins (BoNTs) is primarily a consequence of their ability to bind to multiple receptors at the same time. BoNTs consist of three distinct domains, a metalloprotease light chain (LC), a translocation domain (HN) and a receptor-binding domain (HC). Here we report the crystal structure of HC/FA, complementing an existing structure through the modelling of a previously unresolved loop which is important for receptor-binding. Our HC/FA structure also contains a previously unidentified disulphide bond, which we have also observed in one of two crystal forms of HC/A1. This may have implications for receptor-binding and future recombinant toxin production.
High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA.,Davies JR, Hackett GS, Liu SM, Acharya KR PeerJ. 2018 Mar 21;6:e4552. doi: 10.7717/peerj.4552. eCollection 2018. PMID:29576992[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Davies JR, Hackett GS, Liu SM, Acharya KR. High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA. PeerJ. 2018 Mar 21;6:e4552. doi: 10.7717/peerj.4552. eCollection 2018. PMID:29576992 doi:http://dx.doi.org/10.7717/peerj.4552
