Ganglioside-induced adherence of botulinum and tetanus neurotoxins to adducin.
Preincubation of botulinum neurotoxin serotype A, B, or E with ganglioside GT1b was previously found to enhance adherence of botulinum neurotoxin to synapsin I and an approximately 116-kDa bovine brain synaptosomal protein; in contrast, adherence to these two proteins by tetanus neurotoxin required preincubation with GT1b. We have now found that preincubation of the neurotoxins with ganglioside GD3 enhances their adherence to the approximately 116-kDa protein more than that with GT1b. A purified preparation of the water-soluble approximately 116-kDa protein was obtained from bovine brain synaptosomes by preparative column sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis. N-Terminal amino acid sequences were obtained for two tryptic fragments of the approximately 116-kDa protein. These sequences matched with the data bank sequences for beta-adducin, a cytoskeletal protein. The carboxy-terminal tail region of adducin, but not the head region, was adhered to by the neurotoxins. Adherence of the neurotoxin to adducin and synapsin I may facilitate presentation of the neurotoxin to its specific substrate(s).
Schengrund
C L
CL
Department of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
DasGupta
B R
BR
Hughes
C A
CA
Ringler
N J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism*; D001923:Brain Chemistry; D002148:Calmodulin-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000737:chemistry; D005732:Gangliosides / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D012995:Solubility; D013574:Synaptosomes / Q000737:chemistry; D013744:Tetanus Toxin / Q000378:metabolism*; D000099291:Adducins
D001905:Botulinum Toxins; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D005732:Gangliosides; D007457:Iodine Radioisotopes; D013744:Tetanus Toxin; D000099291:Adducins; C016481:trisialoganglioside GT1