Renugopalakrishnan V, Dobbs J C, Collette T W, Carreira L A, Hutson T B, Garduño-Juarez R
Harvard Medical School, Harvard University, Boston, Massachusetts, 02115, USA.
Biochem Biophys Res Commun. 1999 May 19;258(3):653-6. 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 that in vitro forms 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 beta-sheets and beta-turns and lesser amounts of alpha-helical structures. The beta-sheet component presumably plays an important role in the pH-dependent globule-fibril transformation of HPTP leading to antiparallel beta-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.
利用傅里叶变换红外（FT-IR）和激光拉曼光谱研究推导了酸性pH条件下溶液中人类胰腺丝蛋白（HPTP）的二级结构。将实验推导得到的HPTP二级结构与通过Chou-Fasman算法获得的二级结构进行了比较。胰腺丝蛋白是一种主要的外分泌蛋白，在体外形成的丝状束类似于阿尔茨海默病（AD）的双螺旋丝。先前已证明AD患者大脑中存在PTP免疫反应性，文献中也报道了其在发育中的人类大脑中高水平的mRNA。上述研究表明，AD与PTP相关转录本的表达增强以及PTP样蛋白在神经元间的积累有关。实验推导得到的HPTP二级结构由相当比例的β-折叠和β-转角以及少量的α-螺旋结构组成。β-折叠成分可能在HPTP的pH依赖性球状-纤维转变中起重要作用，导致聚集状态下的反平行β-折叠结构。HPTP的二级结构及其球状-纤维转变支持了AD可被视为一种构象性疾病的观点。
