Dangi Abha, Balmik Abhishek Ankur, Ghorpade Archana Kisan, Gorantla Nalini Vijay, Sonawane Shweta Kishor, Chinnathambi Subashchandrabose, Marelli Udaya Kiran
Central NMR Facility, CSIR-National Chemical Laboratory Dr HomiBhabha Road 411008 Pune India.
Division of Organic Chemistry, CSIR-National Chemical Laboratory Dr HomiBhabha Road 411008 Pune India.
RSC Adv. 2020 Jul 21;10(46):27331-27335. doi: 10.1039/d0ra03809a.
In Alzheimer's disease and related tauopathies, the aggregation of microtubule-associated protein, Tau, into fibrils occurs the interaction of two hexapeptide motifs PHF* VQIINK and PHF VQIVYK as β-sheets. To understand the role of the constituent amino acids of PHF and PHF* in the aggregation, a set of 12 alanine mutant peptides was synthesized by replacing each amino acid in PHF and PHF* with alanine and they were characterized by nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), transmission electron microscopy (TEM) and ThS/ANS fluorescence assay. Our studies show that while the aggregation was suppressed in most of the alanine mutant peptides, replacement of glutamine by alanine in both PHF and PHF* enhanced the fibrillization.
在阿尔茨海默病及相关的tau蛋白病中，微管相关蛋白Tau会聚集成原纤维，这是由两个六肽基序PHFVQIINK和PHF VQIVYK作为β折叠相互作用导致的。为了了解PHF和PHF中组成氨基酸在聚集过程中的作用，通过将PHF和PHF中的每个氨基酸替换为丙氨酸，合成了一组12种丙氨酸突变肽，并通过核磁共振（NMR）光谱、圆二色性（CD）、透射电子显微镜（TEM）和硫黄素T/8-苯胺基-1-萘磺酸（ThS/ANS）荧光测定对它们进行了表征。我们的研究表明，虽然大多数丙氨酸突变肽的聚集受到抑制，但在PHF和PHF中用丙氨酸替换谷氨酰胺会增强纤维化。
