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 neuro nes within the spinal cord, An initial stage in the toxin's action is bindi ng to acceptors on the nerve surface and polysialogangliosides are a compon ent of these acceptor moieties, Using site-directed mutagenesis, we identif y tyrosine-1290 of tetanus toxin as a key residue that is involved in gangl ioside binding, This residue, which is located at the centre of a shallow p ocket on the beta -trefoil domain of the tetanus H-c fragment, is also show n to play a key role in the functional binding of tetanus toxin to spinal c ord neurones leading to the inhibition of neurotransmitter release. (C) 200 1 Published by Elsevier Science B.V. on behalf of the Federation of Europea n Biochemical Societies.