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 helical propensity of beta-lactoglobulin, a predominantly beta-sheet protein, suggested that the fragments of beta-lactoglobulin can assume the non-native helical conformation. In order to assess this possibility, we synthesized four 17-18-residue peptides corresponding to three beta-strand regions and one helical region (as a control) of beta-lactoglobulin and examined their conformation.


RESULTS
We observed residual helicities of up to 17% in water, by far-UV CD, for all four peptide fragments. The helices could be significantly stabilized by the addition of TFE, and the NMR analyses in a mixture of 50% water/TFE indicated that helical structures are formed in the central region whereas both termini are frayed. Thus, the very same residues that form strands in the native beta-lactoglobulin showed high helical preferences.


CONCLUSIONS
These results stand out from the current general view that peptide fragments isolated from proteins either are unfolded or adopt native-like secondary structures. The implications of the results in the mechanism of protein folding and in designing proteins and peptides are significant.
Kuroda
Y
Y
Protein Engineering Research Institute, Osaka, Japan.
Hamada
D
D
Tanaka
T
T
Goto
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D015195:Drug Design; D007782:Lactoglobulins / Q000737:chemistry* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D007782:Lactoglobulins; D010446:Peptide Fragments