Human pancreatic thread protein, an exocrine thread protein with possible implications to Alzheimer's disease: Secondary structure in solution at acid pH

The secondary structure of human pancreatic thread protein (HPTP) in soluti on at acid pH was derived using Fourier transform infrared (FT-IR) and lase r Raman spectroscopic studies. The experimentally derived secondary structu re of HPTP was compared with the secondary structure obtained by the Chou-F asman algorithm. Pancreatic thread protein is a major exocrine secretory pr otein that in vitro forms filamentous bundles reminiscent of the paired hel ical filaments of Alzheimer's disease (AD). PTP immunoreactivity in brains afflicted with AD has been demonstrated previously and high levels of its m RNA in the developing human brain have also been reported in the literature . The above studies suggest that AD is associated with enhanced expression of PTP-related transcripts with interneuronal accumulation of PTP-like prot eins. The experimentally derived secondary structure of HPTP consists of a significant proportion of beta-sheets and beta-turns and lesser amounts of alpha-helical structures. The beta-sheet component presumably plays an impo rtant role in the pH-dependent globule-fibril transformation of HPTP leadin g to antiparallel beta-sheet structure in the aggregated state. The seconda ry structure of HPTP and its globule-fibril transformation lend credence to the belief that AD may be viewed as a conformational disease. (C) 1999 Aca demic Press.