1H-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 several protein neurotoxins of which structure and structure/activity relationships have been extensively studied. It also contains polypeptides such as Aah STR1, which are not toxic, while having highly similar sequences to fully active toxins. We have determined the solution structure of Aah STR1 by use of conventional two-dimensional NMR techniques followed by distance-geometry and energy minimization. We have demonstrated that, despite its lack of toxicity, Aah STR1 is structurally highly related to anti-mammal scorpion toxins specific for Na+ channels. The calculated structure is composed of a short alpha-helix (residues 26-33) connected by a tight turn to a three-stranded antiparallel beta-sheet (sequences 3-6, 38-41 and 44-48). This beta-sheet is right-handed twisted as usual for such secondary structures. The beta-turn connecting 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.