Neurotoxin Binding Site on the Acetylcholine Receptor
Abstract
This research was designed to 1) develop binding-inhibition assays that could be used to screen compounds that might be effective in inhibiting neurotoxin binding to the acetylcholine receptor (AChR), 2) carry out studies to identify the anionic site on primary sequence of the alpha-subunit to which neurotoxins bind, and 3) determine if antibodies to synthetic receptor peptides might be effective in inhibiting neurotoxin binding to the receptor. A solid phase radioassay was developed alpha-bungarotoxin in (BTX) to purified Torpedo AChR and membrane-bound AChR as a model. In order to gain information on the location of the BTX-binding site on the primary sequence of the alpha-subunit of the AChR, Iodine 125-BTX binding to a 32 amino acid peptide comprising residues 173-204 of the Torpedo alpha-subunit was investigated. It is concluded that this region of the alpha-subunit is a major determinant of the toxin-binding site on the receptor. Binding of Iodine 125-BTX was considerably less to corresponding calf and human 32-mers than to the Torpedo 32-mer. This raises the possibility that the neurotoxins do not have as great an effect on the human receptor and that other constituents of snake venoms contribute more to the toxic effects of the venoms in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1987
- Accession Number
- ADA178469
Entities
People
- Diana Donnelly-roberts
- Maria Gastka
- Thomas L. Lentz
Organizations
- Yale University