Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
复制标题
DOI：
10.1016/j.cell.2006.09.025
复制
发表时间：
2006-10-20
期刊：
影响因子：
64.5
通讯作者：
Shi, Yigong
中科院分区：
文献类型：
--
作者：
Xing, Yongna;Xu, Yanhui;Shi, Yigong
丝氨酸/苏氨酸磷酸酶蛋白磷酸酶2A（PP 2A）在细胞功能的许多方面起着重要的作用，并已被证明是一个重要的肿瘤抑制剂。PP 2A的核心酶包括65 kDa的支架亚基和36 kDa的催化亚基。在这里，我们报告的晶体结构的PP 2A核心酶结合到它的两个抑制剂，肿瘤诱导剂冈田酸和微囊藻毒素-LR，在2.6和2.8埃的分辨率，分别。催化亚基通过与HEAT重复序列11-15的保守脊相互作用识别伸长的支架亚基的一端。核心酶的形成迫使支架亚基经历明显的结构重排。支架亚基表现出相当大的构象灵活性，这是建议发挥重要作用的PP 2A功能。这些结构与生化分析一起揭示了PP 2A功能的重要见解，并作为破译PP 2A在细胞生理学中的各种作用的框架。
The serine/threonine phosphatase protein phosphatase 2A (PP2A) plays an essential role in many aspects of cellular functions and has been shown to be an important tumor suppressor. The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. Here we report the crystal structures of the PP2A core enzyme bound to two of its inhibitors, the tumor-inducing agents okadaic acid and microcystin-LR, at 2.6 and 2.8 angstrom resolution, respectively. The catalytic subunit recognizes one end of the elongated scaffolding subunit by interacting with the conserved ridges of HEAT repeats 11-15. Formation of the core enzyme forces the scaffolding subunit to undergo pronounced structural rearrangement. The scaffolding subunit exhibits considerable conformational flexibility, which is proposed to play an essential role in PP2A function. These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology.