Tau is a microtubule-associated protein involved in regulation of assembly and spatial organization of microtubule in neurons. However, in pathological conditions, tau monomers assemble into amyloid filaments characterized by the cross-β structures in a number of neurodegenerative diseases known as tauopathies. In this review, we summarize recent progression on the characterization of structures of tau monomer and filament, as well as the dynamic liquid droplet assembly. Our aim is to reveal how post-translational modifications, amino acid mutations, and interacting molecules modulate the conformational ensemble of tau monomer, and how they accelerate or inhibit tau assembly into aggregates. Structure-based aggregation inhibitor design is also discussed in the context of dynamics and heterogeneity of tau structures.

Tau是与微管相关的蛋白质，参与调节神经元中微管的组装和空间组织。然而，在病理条件下，tau单体组装成淀粉状蛋白丝，其特征在于许多神经退行性疾病（称为tauopathies）中的交叉β结构。在这篇综述中，我们总结了关于tau单体和长丝结构以及动态液滴组装的表征的最新进展。我们的目的是揭示翻译后修饰，氨基酸突变和相互作用的分子如何调节tau单体的构象整体，以及它们如何促进或抑制tau组装成聚集体。还基于tau结构的动力学和异质性讨论了基于结构的聚集抑制剂设计。