Botulinum Neurotoxins B and E Translocate at Different Rates and Exhibit Divergent Responses to GT1b and Low pH
| Autor: | Shihu Sun, Edwin R. Chapman, William H. Tepp, Eric A. Johnson |
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| Rok vydání: | 2012 |
| Předmět: |
Botulinum Toxins
A serotype Chromosomal translocation Hippocampus Biochemistry Protein Structure Secondary Article Microbiology Cytosol Gangliosides medicine Animals Botulism Botulinum Toxins Type A Receptor Protein secondary structure Cells Cultured Neurons Chemistry Hydrogen-Ion Concentration medicine.disease Molecular biology Rats Transport protein Kinetics Protein Transport Proton-Translocating ATPases Convergent and divergent production Macrolides Protein Multimerization Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Biochemistry |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi3004928 |
| Popis: | Botulinum neurotoxins (BoNTs, serotypes A–G) are the most deadly substances known. Here, we investigated how BoNT/E, a serotype that causes human botulism, translocates into the cytosol of neurons. Analogous to BoNT/B, BoNT/E required binding of the coreceptor, GT1b, to undergo significant secondary structural changes and transform into a hydrophobic protein at low pH. These data indicate that both serotypes act as coincidence detectors for both GT1b and low pH, to undergo translocation. However, BoNT/E translocated much more rapidly than BoNT/B. Also, BoNT/E required only GT1b, and not low pH, to oligomerize, whereas BoNT/B required both. In further contrast to the case of BoNT/B, low pH alone altered the secondary structure of BoNT/E to some degree and resulted in its premature inactivation. Hence, comparison of two BoNT serotypes revealed that these agents exhibit both convergent and divergent responses to receptor interactions, and pH, in the translocation pathway. |
| Databáze: | OpenAIRE |
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