Background

Phosphotyrosine Binding (PTB) Domains, usually found on scaffold proteins, are pervasive in many cellular signaling pathways. These domains are the second-largest family of phosphotyrosine recognition domains and since their initial discovery, dozens of PTB domains have been structurally determined.

Scope of review

Due to its signature sequence flexibility, PTB domains can bind to a large variety of ligands including phospholipids. PTB peptide binding is divided into classical binding (canonical NPXY motifs) and non-classical binding (all other motifs). The first atypical PTB domain was discovered in cerebral cavernous malformation 2 (CCM2) protein, while only one third in size of the typical PTB domain, it remains functionally equivalent.

Major conclusions

PTB domains are involved in numerous signaling processes including embryogenesis, neurogenesis, and angiogenesis, while dysfunction is linked to major disorders including diabetes, hypercholesterolemia, Alzheimer's disease, and strokes. PTB domains may also be essential in infectious processes, currently responsible for the global pandemic in which viral cellular entry is suspected to be mediated through PTB and NPXY interactions.

General significance

We summarize the structural and functional updates in the PTB domain over the last 20 years in hopes of resurging interest and further analyzing the importance of this versatile domain.

中文翻译：

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磷酸酪氨酸结合域的复兴：对理解疾病发病机制必不可少的结构和功能特性

背景

磷酸酪氨酸结合 (PTB) 域，通常在支架蛋白上发现，在许多细胞信号通路中普遍存在。这些域是磷酸酪氨酸识别域的第二大家族，自从它们最初被发现以来，已经在结构上确定了数十个 PTB 域。

审查范围

由于其特征序列的灵活性，PTB 结构域可以与包括磷脂在内的多种配体结合。PTB 肽结合分为经典结合（经典 NPXY 基序）和非经典结合（所有其他基序）。第一个非典型 PTB 结构域是在脑海绵状血管瘤 2 (CCM2) 蛋白中发现的，虽然只有典型 PTB 结构域的三分之一大小，但它在功能上仍然相同。

主要结论

PTB 域参与许多信号传导过程，包括胚胎发生、神经发生和血管生成，而功能障碍与糖尿病、高胆固醇血症、阿尔茨海默病和中风等主要疾病有关。PTB 域在感染过程中也可能是必不可少的，目前导致全球大流行，其中怀疑病毒细胞进入是通过 PTB 和 NPXY 相互作用介导的。

一般意义

我们总结了过去 20 年来 PTB 领域的结构和功能更新，希望重新引起人们的兴趣并进一步分析这个多功能领域的重要性。