A LINEAR 23-RESIDUE PEPTIDE REVEALS A PROPENSITY TO FORM AN UNUSUAL NATIVE-LIKE CONFORMATION

To gain insight into the earliest events of protein folding, a 23-resi due peptide with a sequence corresponding to the 38-60 fragment of the beta-subunit of human chorionic gonadotropin (hCG beta) was studied b y NMR. In aqueous solution the majority of the peptide residues adopte d an extended polyproline II (P-II) conformation similar to those in m ature, fully folded hCG beta. The finding that the isolated protein fr agment may acquire native-like structural motifs, even without alpha-h elices or beta-structures, extends the possibility of using free pepti des as model systems to better understand the protein folding mechanis ms. It was shown that the P-II-rich structural motif can be determined efficiently by NMR spectroscopy. The observation that in the absence of extensive medium- and long-range interactions the majority of amino acid residues may adopt the P-II conformation suggests that the P-II- rich structural motifs may play an important role in early events of p rotein folding.