Define Assembly Features of STRIPAK Complex

Striatin interacting phosphatase and kinase (STRIPAK) is a recently identified supramolecular complex, in which striatins act as both a novel type of PP2A regulatory subunit and a scaffold protein to recruit phosphatase such as PP2A and kinases such as germinal center kinases (GCKs) MST1/2, MST3, MST4 and STK25. The STRIPAK complex plays important roles in signaling transduction, cell cycle, apoptosis and polarity, as well as in neural and cardiovascular development. Recently, researchers from Chinese Academy of Sciences revealed assembly features of the STRIPAK complex.

CHEN Cuicui and her colleagues from a research group led by Prof. ZHOU Zhaocai at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS determined the crystal structure of striatins coiled coil domain, and found that it forms a noncanonical asymmetric parallel homodimer, in which one chain contains a large bend. The noncanonical coiled coil directly interacts with PP2A A subunits to form a 2:2 heterotetrameric core of the STRIPAK complex, suggesting that striatin-mediated PP2A holoenzyme is a 2:2:2 heterohexamer, not a canonical heterotrimer. Structure-guided mutational studies further revealed that homodimerization of striatin is required for its interaction with PP2A. Wild-type striatin but not the mutants defective in PP2A binding strongly suppresses MST3-induced apoptosis of Jurkat cells, most likely through a mechanism in which striatin recruits PP2A to negatively regulate the activation of MST3. This work provides structural insights into the organization of the STRIPAK complex that may facilitate further functional studies.

This work entitled “Striatins Contain a Noncanonical Coiled Coil That Binds PP2A A to Form a 2:2 Heterotetrameric Core of Striatin-interacting Phosphatase and Kinase (STRIPAK) Complex” was published online in the Journal of Biological Chemistry on February 18^th, 2014.

This study was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality.

A schematic model of the STRIPAK complex. (Image by Prof. ZHOU Zhaocai’s group)