Université de Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
Adv Exp Med Biol. 2019;1184:35-45. doi: 10.1007/978-981-32-9358-8_3.
Although Tau is an intrinsically disordered protein, some level of structure can still be defined, corresponding to short stretches of dynamic secondary structures and a preferential global fold described as an ensemble of conformations. These structures can be modified by Tau phosphorylation, and potentially other post-translational modifications. The analytical capacity of Nuclear Magnetic Resonance (NMR) spectroscopy provides the advantage of offering a residue-specific view of these modifications, allowing to link specific sites to a particular structure. The cis or trans conformation of X-Proline peptide bonds is an additional characteristic parameter of Tau structure that is targeted and modified by prolyl cis/trans isomerases. The challenge in molecular characterization of Tau lies in being able to link structural parameters to functional consequences in normal functions and dysfunctions of Tau, including potential misfolding on the path to aggregation and/or perturbation of the interactions of Tau with its many molecular partners. Phosphorylation of Ser and Thr residues has the potential to impact the local and global structure of Tau.
尽管 Tau 是一种固有无序的蛋白质，但仍可以定义一定程度的结构，对应于短的动态二级结构延伸和描述为构象集合的优先全局折叠。这些结构可以通过 Tau 磷酸化以及潜在的其他翻译后修饰进行修饰。核磁共振（NMR）光谱的分析能力提供了提供这些修饰的残基特异性视图的优势，允许将特定位点与特定结构相关联。X-Proline 肽键的顺式或反式构象是 Tau 结构的另一个特征参数，脯氨酰顺/反异构酶靶向并修饰该参数。在 Tau 的分子特征描述中面临的挑战是能够将结构参数与 Tau 的正常功能和功能障碍中的功能后果联系起来，包括在聚集的路径上潜在的错误折叠和/或 Tau 与其许多分子伴侣的相互作用的干扰。丝氨酸和苏氨酸残基的磷酸化有可能影响 Tau 的局部和整体结构。
