H-1-NMR-DERIVED SECONDARY STRUCTURE AND OVERALL FOLD OF A NATURAL ANATOXIN FROM THE SCORPION ANDROCTONUS-AUSTRALIS-HECTOR

The venom of the scorpion Androctonus australis hector contains severa l protein neurotoxins of which structure and structure/activity relati onships have been extensively studied. It also contains polypeptides s uch as Aah STR1, which are not toxic, while having highly similar sequ ences to fully active toxins. We have determined the solution structur e of Aah STR1 by use of conventional two-dimentional NMR techniques fo llowed by distance-geometry and energy minimization. We have demonstra ted that, despite its lack of toxicity, Aah STR1 is structurally highl y related to anti-mammmal scorpion toxins specific for Na+ channels. T he calculated structure is composed of a short alpha-helix (residues 2 6-33) connected by a tight rum to a three-stranded antiparallel beta-s heet (sequences 3-6, 38-41 and 44-48). This beta-sheet is right-handed twisted as usual for such secondary structures, The beta-turn connect ing the strands 38-41 and 44-48 belongs to type II'. The overall fold of Aah STR1 is typical of beta-type scorpion toxins. This is, however. the first example of such a fold in Old World scorpion toxins. Either the absence of a basic residue in position 63 or the high mobility of loops, compared to active beta-type neurotoxins, may explain the lack of activity of this protein.