Precursors of Androctonus australis Scorpion Neurotoxins. Structures of Precursors, Processing Outcomes, and Expression of a Functional Recombinant Toxin II

摘要

WE isolated full-length cDNA clones encoding Androctonu s australis scorpion neurotoxins active in mammals or insects. Sequence analysis of the cDNAs revealed that precursors of toxins contained signal peptides of about 20 amino acids. In addition, the scorpion neurotoxins active on mammals had diverse peptide extensions at their C-terminal ends. Accordingly, the processing steps required for maturation into native toxins were not identical for all of the Androctonus australis neurotoxins. Southern blot analysis, performed at the genomic level with toxin II cDNA, seems to indicate that these toxin genes are unique. Finally, as the first successful attempt to express animal toxins, we demonstrated that monkey kidney COS-7 cells transfected with a toxin Ii cDNA clone transiently expressed a biologically active recombinant toxin. For improved serotherapy and possible vaccine development, we wished to pursue the study of structure-activity relationships of scorpion neurotoxins by carrying out specific amino acid substitutions in neurotoxin molecules by using recombinant DNA techniques. As a first step forward and considering also the lack of knowledge on the molecular biology of scorpion neurotoxins, we cloned and sequenced several cDNAs encoding diverse Androctonus australis scorpion neurtoxins. Based on the deduced primary structures and the directly determined amino acid sequences of the native toxins, the structures of toxin precursors suggested multiple post-translational processing steps. Keywords: Toxin and antitoxins. (KT)