Human Pancreatic Thread Protein, an Exocrine Thread Protein with Possible Implications to Alzheimer's Disease: Secondary Structure in Solution at Acid pH

• Published in: Biochemical and biophysical research communications 1999-05, Vol.258 (3), p.653-656
• Main Authors: Renugopalakrishnan, V., Dobbs, J.C., Collette, T.W., Carreira, L.A., Hutson, T.B., Garduño-Juarez, R.
• Format: Article
• Language: English
• Subjects: Algorithms; Alzheimer Disease - metabolism; Amino Acid Sequence; Brain - metabolism; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - metabolism; human pancreatic thread protein; Humans; Hydrogen-Ion Concentration; Lithostathine; Nerve Tissue Proteins; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0667

The secondary structure of human pancreatic thread protein (HPTP) in solution at acid pH was derived using Fourier transform infrared (FT-IR) and laser Raman spectroscopic studies. The experimentally derived secondary structure of HPTP was compared with the secondary structure obtained by the Chou-Fasman algorithm. Pancreatic thread protein is a major exocrine secretory protein thatin vitroforms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD). PTP immunoreactivity in brains afflicted with AD has been demonstrated previously and high levels of its mRNA 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 proteins. The experimentally derived secondary structure of HPTP consists of a significant proportion of β-sheets and β-turns and lesser amounts of α-helical structures. The β-sheet component presumably plays an important role in the pH-dependent globule–fibril transformation of HPTP leading to antiparallel β-sheet structure in the aggregated state. The secondary structure of HPTP and its globule–fibril transformation lend credence to the belief that AD may be viewed as a conformational disease.