Abstract
the secondary structure of a synthetic peptide representing the NH2-terminal, precursor-specific extension sequence of preproparathyroid hormone was studied. NH2-terminal extensions, or leader sequences, may serve a critical role in determining and facilitating the cellular secretion of proteins. These precursor regions, including the synthetic hormonal fragment studied, share common features of amino acid sequence and also may be similar in secondary structure. The secondary structure of the synthetic precursor peptide was predicted as described [Chou, P. Y. & Fasman, G. D. (1978) Adv. Enzymol. 47, 45-148]. The secondary structure was derived from circular dichroism spectra in both an aqueous buffer at physiological pH and in a nonpolar solvent selected to approximate the intramembranous environment. Two highly structured conformations were observed. In the aqueous buffer the secondary structure was 27% alpha-helix, 43% beta-sheet, and 30% random coil. In the nonpolar solvent the secondary structure was 46% alpha-helix, 0% beta-sheet, and 54% random coil. These findings correlated well with the two highest-probability structures predicted from the amino acid sequence. Both the relatively high content of secondary structure in a peptide of this size (30 amino acids) and the conformational transition observed in changing from aqueous to nonpolar environments may reflect structural properties critical to the physiological function of NH2-terminal extension sequences, and both are consistent with current theories regarding the role of precursor regions in the intracellular transport and secretion of proteins.