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 toxin's 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 beta-trefoil domain of the tetanus H(c) 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.
Sutton
J M
JM
Centre for Applied Microbiology and Research (CAMR), Porton Down, SP4 0JG, Salisbury, UK.
Chow-Worn
O
O
Spaven
L
L
Silman
N J
NJ
Hallis
B
B
Shone
C C
CC
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D013744:Tetanus Toxin / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry* / Q000502:physiology*
D005732:Gangliosides; D008024:Ligands; D013744:Tetanus Toxin; D014443:Tyrosine; D011188:Potassium