化学
脂质双层
膜
生物物理学
费斯特共振能量转移
荧光相关光谱
纤维
磷脂酰丝氨酸
小泡
单体
构象变化
τ蛋白
生物膜
分子间力
结晶学
分子
磷脂
生物化学
荧光
生物
阿尔茨海默病
病理
物理
量子力学
有机化学
聚合物
疾病
医学
作者
Qiong-Qiong Yao,Jitao Wen,Sarah Perrett,Si Wu
出处
期刊:Nanoscale
[The Royal Society of Chemistry]
日期:2022-01-01
卷期号:14 (12): 4604-4613
被引量:12
摘要
The conversion of intrinsically disordered Tau to highly ordered amyloid aggregates is associated with a wide range of neurodegenerative diseases termed tauopathies. The presence of lipid bilayer membranes is a critical factor that accelerates the abnormal aggregation of Tau protein. However, the lipid membrane-induced conformational changes of Tau and the mechanism for the accelerated fibrillation remain elusive. In this study, single-molecule Förster resonance energy transfer (smFRET) and fluorescence correlation spectroscopy (FCS) were applied to detect the conformational changes and intermolecular interactions of full-length Tau in the presence of different concentrations of 1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) vesicles. The results show that the conformation of Tau becomes expanded with opening of the N-terminal and C-terminal domains of Tau upon binding to DMPS. At low DMPS concentrations, Tau forms oligomers with a partially extended conformation which facilitates the amyloid fibrillization process. At high DMPS concentrations, Tau monomer binds to lipid membranes in a fully expanded conformation at low density thus inhibiting intermolecular aggregation. Our study reveals the underlying mechanisms by which lipid membranes influence amyloid formation of Tau, providing a foundation for further understanding of the pathogenesis and physiology of the interplay between Tau protein and lipid membranes.
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