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J. Biol. Chem., Vol. 265, Issue 16, 9153-9158, Jun, 1990
The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins
T Binz, H Kurazono, M Wille, J Frevert, K Wernars and H Niemann
Institut fur Medizinische Virologie der Justus-Liebig-Universitat, Giessen, Federal Republic of Germany.
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.

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Copyright © 1990 by the American Society for Biochemistry and Molecular Biology.
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