The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin.
Tetanus toxin, a member of the family of Clostridial neurotoxins, is one of the most potent toxins known. The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the ganglioside-binding sites. The ganglioside induces cross-linking by binding to two distinct sites on the Hc molecule. The structure sheds new light on the binding of Clostridial neurotoxins to receptors on neuronal cells and provides important information relevant to the design of anti-tetanus and anti-botulism therapeutic agents.
Fotinou
C
C
Department of Chemistry, University of Glasgow, Glasgow, G12 8QQ, Scotland, United Kingdom.
Emsley
P
P
Black
I
I
Ando
H
H
Ishida
H
H
Kiso
M
M
Sinha
K A
KA
Fairweather
N F
NF
Isaacs
N W
NW
D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry*; D013744:Tetanus Toxin / Q000737:chemistry*
D005732:Gangliosides; D011956:Receptors, Cell Surface; D013744:Tetanus Toxin; C034993:ganglioside receptor; C016481:trisialoganglioside GT1