Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside
| العنوان: | Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside |
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| المؤلفون: | K. Ravi Acharya, Kyle S. Gregory, Sai Man Liu |
| المصدر: | FEBS Open Bio FEBS Open Bio, Vol 10, Iss 3, Pp 298-305 (2020) |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Co-receptor, Botulinum Toxins, ganglioside binding, cell binding domain, Immunoglobulin light chain, medicine.disease_cause, Crystallography, X-Ray, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Protein Domains, Ganglioside binding, Gangliosides, medicine, Humans, protein structure, Botulinum Toxins, Type A, Receptor, crystallography, lcsh:QH301-705.5, Research Articles, Neurons, Ganglioside, Binding Sites, Chemistry, Hydrogen bond, Toxin, Cell Membrane, botulinum neurotoxin, 030104 developmental biology, lcsh:Biology (General), 030220 oncology & carcinogenesis, Biophysics, Carrier Proteins, Research Article, Protein Binding |
| الوصف: | Botulinum neurotoxins (BoNTs) are one of the most toxic proteins known to humans. Their molecular structure is comprised of three essential domains—a cell binding domain (HC), translocation domain and catalytic domain (light chain) . The HC domain facilitates the highly specific binding of BoNTs to the neuronal membrane via a dual‐receptor complex involving a protein receptor and a ganglioside. Variation in activity/toxicity across subtypes of serotype A has been attributed to changes in protein and ganglioside interactions, and their implications are important in the design of novel BoNT‐based therapeutics. Here, we present the structure of BoNT/A3 cell binding domain (HC/A3) in complex with the ganglioside GD1a at 1.75 Å resolution. The structure revealed that six residues interact with the three outermost monosaccharides of GD1a through several key hydrogen bonding interactions. A detailed comparison of structures of HC/A3 with HC/A1 revealed subtle conformational differences at the ganglioside binding site upon carbohydrate binding. The majority of botulinum neurotoxin (BoNT) serotypes require recognition of both the protein and the ganglioside receptor to gain entry in to the cell. Here, we show that the cell binding domain of BoNT A3 binds three monosaccharides of GD1a receptor. Six residues of the protein interact with this receptor through several key hydrogen bonding interactions. |
| اللغة: | English |
| تدمد: | 2211-5463 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2cc402b96998c7bbc0608ec0135316f http://europepmc.org/articles/PMC7050238 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b2cc402b96998c7bbc0608ec0135316f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22115463 |
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