Protein Receptor(s) of Botulinum Neurotoxin
Abstract
Seven serotypes of botulinum neurotoxin (BoNT) are a group of water-soluble large proteins that act on the presynaptic nerve cells of the neuro-muscular junctions. BoNTs act intracellulary to block acetylcholine neurotransmitter release leading to the flaccid muscle paralysis in the dreaded botulism disease. In order to enter the neuronal cells, BoNTs bind to as yet to be clearly identified protein receptor(s), which could be targeted to develop proper antidotes. The aim of this research has been to identify protein receptor(s) of BoNTs by purifying them from neuronal tissues, and characterize its binding mechanism with the neurotoxins, including the effects of low pH and membrane lipid interactions. During the past three years, we have made major strides in discovering the domain of receptor that binds to the BoNT/A and /E, a novel form of BoNT/E, interaction of native and purified BoNTs to the a potential receptor protein, GT1b-induced structural changes in purified BoNT/E and its light chain, role of receptor in the translocation of the toxin, differential binding of the identified receptor with different serotypes of BoNT, identification of a component within BoNT complex that effectively binds to nerve membrane, and a surprise survival of quahogs with exposure to heavy doses of BoNT. In addition, we have improved methodologies to examine structural changes in BoNT proteins. These results have been communicated through 8 published article, 2 pending publications, and over 35 conference presentations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA437753
Entities
People
- Bal R. Singh
Organizations
- University of Massachusetts