Step-wise formation of helical structure and side-chain packing in a peptide from scorpion neurotoxin support hierarchic model of protein folding

The mechanism of protein folding has been the subject of extensive investig ation during the last decade, both because of its academic challenge and be cause of its relation to many diseases which are known to occur due to misf olding of proteins. In this context, we report here a systematic investigat ion on the step-wise formation of a helical structure by the addition of he xafluoroacetone, in a 14-residue peptide derived from a part of the scorpio n neurotoxin protein. The NMR and circular dichroism results indicate that the peptide has an inherent propensity for helix formation and this is limi ted to the internal few residues in aqueous solution. With the addition of the fluorosolvent, the helical content progressively increases and spans th e whole sequence. This is accompanied by concomitant packing of the side ch ains. These results provide support to the so-called hierarchic model of pr otein folding which dictates that the local sequence determines the seconda ry structures in the protein and the side chains play an important role in this process. (C) 2000 Elsevier Science B.V. All rights reserved.