2024年2月15日 · Fyn kinase SH3 domain interaction with PXXP motif in the Tau protein is implicated in AD pathology and is central to NMDAR function. Among seven PXXP motifs localized in proline-rich domain of Tau protein, tandem 5th and 6th PXXP motifs are critical to Fyn-SH3 domain interaction.

2020年2月1日 · To determine whether the beneficial effects of Tau reduction would be replicated by inhibiting Tau-SH3 interactions, we developed a cell-permeable Tau-SH3 interaction inhibitor peptide (Tau-PxxP 5/6) based on a 17–amino acid peptide spanning the 5th and 6th PxxP motifs of the proline-rich domain of human Tau protein (amino acids 209–225 ...

通过MBD结合微管能够引起Tau蛋白的结构改变，使得负电荷区域从微管表面产生分支，形成一个链接基团 (linker)与如 膜联蛋白 等膜组分连接在一起。 脯氨酸富集区的序列包括PxxP基序。 较短的碳端功能区似乎可以抑制Tau蛋白聚合，这段区域的缺失可能与Tau蛋白在AD中的丝状结构形成有关。 图2 人类中枢神经系统六种Tau蛋白亚型序列及四大功能区分布 (图片来源：参考文献2) Tau蛋白的病理生理学. 研究发现Tau蛋白的 翻译后修饰 (post-translational modifications, …

在这里，我们报告了由第 5 个和第 6 个 pxxp 基序复合物组成的 fyn-sh3 -tau (207–221) 肽的晶体结构，分辨率为 1.01 Å。在包含第 5 个和第 6 个 pxxp 基序的 5 个 ad 特异性磷酸化位点中，只有 s214 残基显示出与 sh3 结构域的相互作用。

2023年8月10日 · Tau-S214 Phosphorylation Inhibits Fyn Kinase Interaction and Increases the Decay Time of NMDAR-mediated Current. Fyn kinase SH3 domain interaction with PXXP motif in the Tau protein is implicated in AD pathology and is central to NMDAR function.

本研究通过晶体结构分析和生物物理学实验，发现Tau蛋白中的第五和第六个PXXP基序对于Fyn-SH3域的相互作用至关重要。 在七个PXXP基序中，这两个基序是与Fyn-SH3域相互作用的关键。

The aberrant assembly of microtubule-associated protein Tau (τ) into insoluble aggregates is closely related to Alzheimer's disease (AD), which is elicited from Tau phosphorylation events and regulated by the specific intermolecular recognition between the proline-rich PxxP motifs of …

2024年2月15日 · Fyn kinase SH3 domain interaction with PXXP motif in the Tau protein is implicated in AD pathology and is central to NMDAR function. Among seven PXXP motifs localized in proline-rich domain of Tau protein, tandem 5th and 6th PXXP motifs are critical to Fyn-SH3 domain interaction.

2017年5月19日 · It can phosphorylate tau at its tyrosine 18 residue to generate pY18-tau and can bind to tau through one or more proline-rich (PxxP) motifs in tau [23,24,25,26,27]. Fyn can also modulate the phenotype of transgenic mice overexpressing human amyloid precursor proteins (hAPP) and hAPP-derived amyloid-β (Aβ) peptides in neurons.

A variety of evidence indicates that Tau’s interactions with Fyn kinase and other SH3 domain–containing proteins, which bind to PxxP motifs in Tau’s proline-rich domain, may contribute to AD deficits and Aβ toxicity. Thus, we sought to determine if inhibiting Tau-SH3 interactions ameliorates Aβ toxicity.