HIGH HELICITY OF PEPTIDE-FRAGMENTS CORRESPONDING TO BETA-STRAND REGIONS OF BETA-LACTOGLOBULIN OBSERVED BY 2D-NMR SPECTROSCOPY

Background: Whereas protein fragments, when they are structured, adopt conformations similar to that found in the native state, the high hel ical propensity of beta-lactoglobulin, a predominantly P-sheet protein , suggested that the fragments of beta-lactoglobulin can assume the no n-native helical conformation. In order to assess this possibility, we synthesized four 17-18-residue peptides corresponding to three beta-s trand regions and one helical region (as a control) of beta-lactoglobu lin and examined their conformation. Results: We observed residual hel icities of up to 17% in water, by far-UV CD, for all four peptide frag ments. The helices could be significantly stabilized by the addition o f TFE, and the NMR analyses in a mixture of 50% water/TFE indicated th at helical structures are formed in the central region whereas both te rmini are frayed. Thus, the very same residues that form strands in th e native beta-lactoglubulin showed high helical preferences. Conclusio ns: These results; stand out from the current general view that peptid e fragments isolated from proteins either are unfolded or adopt native -like secondary structures. The implications of the results in the mec hanism of protein folding and in designing proteins and peptides are s ignificant. (C) Current Biology Ltd