在8月18日的Molecular Cell（分子细胞）杂志上，来自美国普林斯顿大学Lewis Thomas实验室的华人科学家施一公（Yigong Shi）的研究组破译了PTPA（磷酸酪氨酸磷酸酶活化因子）的结构和作用机制。
酪氨酸磷酸酯酶活化因子（PTPA）也叫做PP2A（蛋白磷酸酯酶2A）磷酸酶活化因子。它是一种从酵母到人类都存在的保守蛋白质。在这项新的研究中，研究人员描述了人类PTPA的结构（分辨率为1.9 Å）。该结构揭示出了一个之前未知的三个亚结构域：核、lid和连接体。
结构分析发现了一种高度保守的表面“补丁”，它与三个亚结构域接壤。此外，还有一个相关的深“口袋”位于核和连接体亚结构域之间。这种保守的表面补丁和深口袋负责分别与PP2A和ATP结合。PTPA和PP2A A-C二聚体共同构成一种复合的ATP酶。PTPA与PP2A结合会导致底物特异性的巨大变化，并且会提高磷酸酪氨酸磷酸酶的活性并降低磷酸丝氨酸磷酸酶的活性。
PTPA的功能紧紧依赖ATP酶活性。这些观察结果使研究人员得以更深入地了解PTPA的功能和作用机制，并且将有助于了解PP2A的功能。
部分英文原文：
Structure and Mechanism of the Phosphotyrosyl Phosphatase Activator
Phosphotyrosyl phosphatase activator (PTPA), also known as PP2A phosphatase activator, is a conserved protein from yeast to human. Here we report the 1.9 Å crystal structure of human PTPA, which reveals a previously unreported fold consisting of three subdomains: core, lid, and linker. Structural analysis uncovers a highly conserved surface patch, which borders the three subdomains, and an associated deep pocket located between the core and the linker subdomains. The conserved surface patch and the deep pocket are responsible for binding to PP2A and ATP, respectively. PTPA and PP2A A-C dimer together constitute a composite ATPase. PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity. This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function.
相关报道：
细胞生长检测7：碱性磷酸酶检测法（AKP法）
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