The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins.
The seven serologically different botulinum neurotoxins are highly potent protein toxins that inhibit neurotransmitter release from peripheral cholinergic synapses. The activated toxins consist of the toxifying A-subunits (Mr approximately 50,000) linked by a disulfide bond to the receptor-binding BC-subunits (Mr approximately 100,000). We have established the complete sequence of botulinum neurotoxin type A (BoNT/A; 1,296 amino acid residues, Mr = 149,425) and a partial sequence of botulinum neurotoxin type E (273 amino acid residues) as deduced from the corresponding nucleotide sequences of the chromosomally located structural genes. The promoter of the BoNT/A gene is inactive in Escherichia coli. Primer extension experiments indicated that initiation of transcription of the BoNT/A gene occurred 118 nucleotides upstream from the ATG codon. A comparison of the protein sequence revealed an overall identity of 33.8% to that of tetanus toxin. No significant similarity to other known proteins including ADP-ribosylating toxins could be detected. Three of the six histidine residues of the A-subunit of BoNT/A were found in the peptide sequence H223ELIHXXH230 within a domain of predicted alpha-helical secondary structure. This motif is also found in similar positions of the A-subunits of tetanus toxin and BoNT/E.
Binz
T
T
Institut für Medizinische Virologie der Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
Kurazono
H
H
Wille
M
M
Frevert
J
J
Wernars
K
K
Niemann
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D001905:Botulinum Toxins / Q000235:genetics; D003014:Clostridium botulinum / Q000235:genetics; D003062:Codon; D004262:DNA Restriction Enzymes; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D013744:Tetanus Toxin / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D003062:Codon; D004269:DNA, Bacterial; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D013744:Tetanus Toxin; D004262:DNA Restriction Enzymes; D001905:Botulinum Toxins