Article
Biochemistry & Molecular Biology
Fodil Azzaz, Didier Hilaire, Jacques Fantini
Summary: This study investigated the molecular mechanisms of botulinum neurotoxin BoNT/F1 binding to its membrane receptor SV2A. It was found that the interaction between BoNT/F1 and SV2A is mediated exclusively by the N-glycan moiety, independent of the protein content of SV2A. Additionally, structural elements were identified suggesting that BoNT/F1 combines the strategies of BoNT/A1 and BoNT/E to bind to the N-glycan of its glycoprotein receptor. These findings provide insights for the design of a universal inhibitor to disrupt N-glycan-toxin interactions and the bioengineering of BoNT/F1 protein for therapeutic purposes.
Article
Biochemistry & Molecular Biology
Geoffrey Masuyer, Jonathan R. Davies, Pal Stenmark
Summary: Botulinum neurotoxins are potent molecules that cause botulism and are also used for therapeutic purposes. This study focused on the binding domain of BoNT/E and its interaction with the GD1a oligosaccharide receptor, revealing unique interacting residues and structural rearrangements upon carbohydrate binding. These findings provide a structural basis for understanding the specificity of BoNT/E for complex gangliosides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Joseph D. Cleveland, Amir Taslimi, Qi Liu, Anna M. Van Keuren, Mair E. A. Churchill, Chandra L. Tucker
Summary: Proteases with reprogrammed specificity for non-native substrates are highly desired in synthetic biology and biomedicine. In this work, researchers engineered an orthogonal botulinum neurotoxin serotype B (BoNT/B) protease that recognizes an orthogonal substrate to expand the versatility of protease systems. They designed and validated an orthogonal BoNT/B protease system in mammalian cells and demonstrated its application in regulating complex transcriptional circuitry. The platform was also successfully applied for in vivo protease evolution in yeast and used to identify novel orthogonal protease/protease substrate combinations through high-throughput screening. In addition, the researchers developed new cleavage reporters for reporting botulinum toxin protease activity in mammalian cells.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zheng Liu, Pyung-Gang Lee, Nadja Krez, Kwok-ho Lam, Hao Liu, Adina Przykopanski, Peng Chen, Guorui Yao, Sicai Zhang, Jacqueline M. Tremblay, Kay Perry, Charles B. Shoemaker, Andreas Rummel, Min Dong, Rongsheng Jin
Summary: The binding and uptake of botulinum neurotoxin E (BoNT/E) requires the glycosylation of its host receptor SV2A with high selectivity for SV2A and SV2B over SV2C. The interaction between BoNT/E and SV2 is mediated through both protein-protein and protein-glycan associations, which are essential for BoNT/E to enter cells and exert neurotoxicity.
NATURE COMMUNICATIONS
(2023)
Article
Food Science & Technology
Shin-Ichiro Miyashita, Shura Karatsu, Mako Fujiishi, I. Hsun Huang, Yuki Nagashima, Tamaki Morobishi, Keita Hosoya, Tsuyoshi Hata, Min Dong, Yoshimasa Sagane
Summary: This study investigated the efficacy of a drug called Botulinum neurotoxin/CD (BoNT/CD) as a potential alternative therapeutic option for patients who do not respond to existing treatments.
Article
Biochemistry & Molecular Biology
Alexander Gardner, William H. Tepp, Marite Bradshaw, Joseph T. Barbieri, Sabine Pellett
Summary: This study investigated the intracellular localization of LC/A3 and LC/A1 in BoNT/A and their impact on potency, finding that the association of LC/A with the plasma membrane contributes to enhanced toxin activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Zhen Li, Jiansheng Lu, Xiao Tan, Rong Wang, Qing Xu, Yunzhou Yu, Zhixin Yang
Summary: In this study, the EL-HN fragment of BoNT/E was found to have high protective efficacy and contain neutralizing epitopes. EL-HN plays an important role in immune protection against BoNT/E and has the potential to be the optimal immunogen for botulinum vaccines.
Article
Food Science & Technology
Baohua Zhao, Zhiying Jin, Yunzhou Yu, Yue Li, Jing Wang, Wei Wan, Chenyi Hu, Xiaoyang Li, Yanwei Li, Wenwen Xin, Lin Kang, Hao Yang, Jinglin Wang, Shan Gao
Summary: In this study, a thermally stable and dissolving microneedle patch for delivering a recombinant protein vaccine against BoNT/A was developed using a fish gelatin matrix. The microneedle patch showed excellent mechanical properties and vaccination effect. The fish gelatin matrix protected the vaccine from protein denaturation under high temperature storage. This microneedle patch has the potential for rapid, painless, and large-scale vaccination.
Article
Pharmacology & Pharmacy
Cindy Perier, Vincent Martin, Sylvie Cornet, Christine Favre-Guilmard, Marie-Noelle Rocher, Julien Bindler, Stephanie Wagner, Emile Andriambeloson, Brian Rudkin, Rudy Marty, Alban Vignaud, Matthew Beard, Stephane Lezmi, Mikhail Kalinichev
Summary: The recombinant BoNT A1 (rBoNT/A1) exhibited similar properties to natural BoNT A1 (nBoNT/A1) in inhibiting motoneurons neurotransmitter release, resulting in long-lasting muscle strength suppression and impaired neurotransmitter release. The study suggests that rBoNT/A1 is a valuable tool for comparing with current and future neurotoxin products.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Biophysics
Veronica Caratelli, Silvia Fillo, Nino D'Amore, Ornella Rossetto, Marco Pirazzini, Maria Moccia, Concetta Avitabile, Danila Moscone, Florigio Lista, Fabiana Arduini
Summary: A paper-based antibody-free sensor has been developed for rapid and reliable detection of BoNT/A and BoNT/C, with a high linear range and low detection limit. Testing with spiked orange juice samples showed that the sensor has high accuracy and reliability in practical applications.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Food Science & Technology
Zhiying Li, Bolin Li, Jiansheng Lu, Xuyang Liu, Xiao Tan, Rong Wang, Peng Du, Shuo Yu, Qing Xu, Xiaobin Pang, Yunzhou Yu, Zhixin Yang
Summary: In this study, the immunoprotective efficacy of two forms of BoNT/F, FL-HN-SC and FL-HN-DC, was investigated. It was found that FL-HN-SC showed better immune protection than the Hc of BoNT/F, indicating its potential as a subunit vaccine. FL-HN-DC could be used to evaluate the structure and activity of toxin molecules.
Article
Biochemistry & Molecular Biology
Fodil Azzaz, Didier Hilaire, Jacques Fantini
Summary: Botulinum neurotoxin A1 (BoNT/A1) is a potent natural poison that binds to the luminal domains of SV2A and SV2C, and the interactions are mediated by glycosylation and N-glycans. The presence of N480g in LD-SV2C enhances the binding of BoNT/A1 to the second N-glycan at position N559g by acting as a shield. The high affinity between BoNT/A1 and LD-SV2C is mediated by a compact structure and specific interactions.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Microbiology
Pengya Gao, Changde Wu, Jin Zhang, Shuping Wang, Ying Huang, Yinping Dong, Tingting Liu, Changyun Ye, Xuefang Xu, Wenwen Xin
Summary: Clostridium botulinum is the causative pathogen of botulism, and its high toxicity requires a sensitive detection method. This study used micro-drop digital PCR to detect more positive samples in clinical samples and shorten the enrichment time, which is important for laboratory diagnosis and epidemiological work.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Nicholas G. James, Shiazah Malik, Bethany J. Sanstrum, Catherine Rheaume, Ron S. Broide, David M. Jameson, Amy Brideau-Andersen, Birgitte S. Jacky
Summary: The study demonstrates that recombinant H(C)/A can induce FGFR dimerization, potentially affecting the function of FGFRs directly or indirectly.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Edanur Sen, Krishna P. Kota, Rekha G. Panchal, Sina Bavari, Erkan Kiris
Summary: BoNT/A is the most studied serotype responsible for most cases of human botulism. Studies have shown that E3 ligase HECTD2 and deubiquitinase VCIP135 play crucial roles in the degradation of BoNT/A, potentially as drug targets for countermeasures against botulism.
FRONTIERS IN PHARMACOLOGY
(2021)