Bassam Hallis

Tyrosine-1290 of tetanus neurotoxin plays a key role in its binding to gangliosides and functional binding to neurones

Tetanus toxin acts by blocking the release of glycine from inhibitory neurones within the spinal cord. An initial stage in the toxins action is binding to acceptors on the nerve surface and polysialogangliosides are a component of these acceptor moieties. Using site‐directed mutagenesis, we identify tyrosine‐1290 of tetanus toxin as a key residue that is involved in ganglioside binding. This residue, which is located at the centre of a shallow pocket on the β‐trefoil domain of the tetanus Hc fragment, is also shown to play a key role in the functional binding of tetanus toxin to spinal cord neurones leading to the inhibition of neurotransmitter release.

Characterization of Monoclonal Antibodies to Botulinum Type A Neurotoxin

The botulinum neurotoxin types primarily involved in human illness are types A, B, E and F. Type A neurotoxin is the most intensively studied of the neurotoxins. However the antigenic sites remain unknown. The aim of the current project is to study the structure and determine the location of the antigenic sites of the type A neurotoxin.