Article ; Online: Biological and Immunological Characterization of a Functional L-HN Derivative of Botulinum Neurotoxin Serotype F.
2023 Volume 15, Issue 3
Abstract: ... that the FL-HN-SC had a better immune protection effect than the Hc of BoNT/F (FHc), which indicated that L-HN ... that there were some important antibody epitopes at the L-HN junction of BoNT/F. Thus, FL-HN-SC could be used ... L, catalytic domain, 50 kDa) and the heavy chain (H, 100 kDa), which can be divided into an N ...
| Abstract | Botulinum neurotoxins (BoNTs) can cause nerve paralysis syndrome in mammals and other vertebrates. BoNTs are the most toxic biotoxins known and are classified as Class A biological warfare agents. BoNTs are mainly divided into seven serotypes A-G and new neurotoxins BoNT/H and BoNT/X, which have similar functions. BoNT proteins are 150 kDa polypeptide consisting of two chains and three domains: the light chain (L, catalytic domain, 50 kDa) and the heavy chain (H, 100 kDa), which can be divided into an N-terminal membrane translocation domain (HN, 50 kDa) and a C-terminal receptor binding domain (Hc, 50 kDa). In current study, we explored the immunoprotective efficacy of each functional molecule of BoNT/F and the biological characteristics of the light chain-heavy N-terminal domain (FL-HN). The two structure forms of FL-HN (i.e., FL-HN-SC: single chain FL-HN and FL-HN-DC: di-chain FL-HN) were developed and identified. FL-HN-SC could cleave the vesicle associated membrane protein 2 (VAMP2) substrate protein in vitro as FL-HN-DC or FL. While only FL-HN-DC had neurotoxicity and could enter neuro-2a cells to cleave VAMP2. Our results showed that the FL-HN-SC had a better immune protection effect than the Hc of BoNT/F (FHc), which indicated that L-HN-SC, as an antigen, provided the strongest protective effects against BoNT/F among all the tested functional molecules. Further in-depth research on the different molecular forms of FL-HN suggested that there were some important antibody epitopes at the L-HN junction of BoNT/F. Thus, FL-HN-SC could be used as a subunit vaccine to replace the FHc subunit vaccine and/or toxoid vaccine, and to develop antibody immune molecules targeting L and HN domains rather than the FHc domain. FL-HN-DC could be used as a new functional molecule to evaluate and explore the structure and activity of toxin molecules. Further exploration of the biological activity and molecular mechanism of the functional FL-HN or BoNT/F is warranted. |
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| MeSH term(s) | Animals ; Botulinum Toxins, Type A/metabolism ; Serogroup ; Vesicle-Associated Membrane Protein 2 ; Neurotoxins/metabolism ; Mammals/metabolism |
| Chemical Substances | botulinum toxin type F (U1R2P71O7G) ; Botulinum Toxins, Type A (EC 3.4.24.69) ; Vesicle-Associated Membrane Protein 2 ; Neurotoxins |
| Language | English |
| Publishing date | 2023-03-06 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2518395-3 |
| ISSN | 2072-6651 ; 2072-6651 |
| ISSN (online) | 2072-6651 |
| ISSN | 2072-6651 |
| DOI | 10.3390/toxins15030200 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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