FOLDING OF PEPTIDE FRAGMENTS OF PROTEINS IN WATER SOLUTION: IMPLICATIONS FOR INITIATION OF PROTEIN FOLDING

Abstract

It is generally accepted that protein folding proceeds via local folded intermediates which function as initiation sites for cooperative growth. However, direct experimental identification of the transient early folding intermediates of native proteins is difficult because, under conditions which favor folding, the polypeptide chain folds rapidly and cooperatively into its native globular conformation. Recent developments in two-dimensional NMR spectroscopy have provided very sensitive methods for the detection of folded structures in peptide fragments of proteins in water solution. NMR experiments have provided unequivocal evidence for the formation of #-turns, nascent helix and a-helix in short linear peptides in water solution. By systematic variation of the amino acid sequence, information on the factors which stabilize secondary structure in small linear peptides can be obtained. The observation that peptide fragments of proteins adopt secondary structures in water solution has enormous implications for initiation of protein folding, for the mechanism of induction of protein-reactive anti-peptide antibodies and for T-cell recognition.