Striatins Contain a Noncanonical Coiled Coil That Binds Protein Phosphatase 2A A Subunit to Form a 2: 2 Heterotetrameric Core of Striatin- interacting Phosphatase and Kinase ( STRIPAK) Complex*
文献类型：期刊论文
| 作者 | Chen, CC; Shi, ZB; Zhang, WQ; Chen, M; He, F; Zhang, ZZ; Wang, YC; Feng, M; Wang, WJ; Zhao, Y |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2014 |
| 卷号 | 289期号:14页码:9651-9661 |
| 关键词 | Apoptosis Phosphatase PP2A Protein Complexes Protein Kinases Protein Structure Coiled Coil Parallel Dimer STRIPAK Complex Striatin |
| 通讯作者 | Jiao, S (reprint author), Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Cell Biol, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,jiaoshi@sibcb.ac.cn ; zczhou@sibcb.ac.cn |
| 英文摘要 | Background: Striatins are novel regulatory subunits of PP2A in the striatin-interacting phosphatase and kinase (STRIPAK) complex. Results: The striatin coiled coil forms a noncanonical dimer required for PP2A A subunit binding. Conclusion: The coiled coil of striatins bind PP2A A subunits to form a 2:2 heterotetrameric core of the STRIPAK complex. Significance: The current structural analysis provides insights into the assembly of the STRIPAK complex. The protein phosphatase 2A (PP2A) and kinases such as germinal center kinase III (GCKIII) can interact with striatins to form a supramolecular complex called striatin-interacting phosphatase and kinase (STRIPAK) complex. Despite the fact that the STRIPAK complex regulates multiple cellular events, it remains only partially understood how this complex itself is assembled and regulated for differential biological functions. Our recent work revealed the activation mechanism of GCKIIIs by MO25, as well as how GCKIIIs heterodimerize with CCM3, a molecular bridge between GCKIII and striatins. Here we dissect the structural features of the coiled coil domain of striatin 3, a novel type of PP2A regulatory subunit that functions as a scaffold for the assembly of the STRIPAK complex. We have determined the crystal structure of a selenomethionine-labeled striatin 3 coiled coil domain, which shows it to assume a parallel dimeric but asymmetric conformation containing a large bend. This result combined with a number of biophysical analyses provide evidence that the coiled coil domain of striatin 3 and the PP2A A subunit form a stable core complex with a 2:2 stoichiometry. Structure-based mutational studies reveal that homodimerization of striatin 3 is essential for its interaction with PP2A and therefore assembly of the STRIPAK complex. Wild-type striatin 3 but not the mutants defective in PP2A binding strongly suppresses apoptosis of Jurkat cells induced by the GCKIII kinase MST3, most likely through a mechanism in which striatin recruits PP2A to negatively regulate the activation of MST3. Collectively, our work provides structural insights into the organization of the STRIPAK complex and will facilitate further functional studies. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | CALMODULIN-BINDING ; NUCLEAR AUTOANTIGEN ; DENDRITIC SPINES ; S-PHASE ; FAMILY ; ACTIVATION ; PP2A ; INSIGHTS ; CAVEOLIN-1 ; MECHANISM |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000333807000019 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/255]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Chen, CC,Shi, ZB,Zhang, WQ,et al. Striatins Contain a Noncanonical Coiled Coil That Binds Protein Phosphatase 2A A Subunit to Form a 2: 2 Heterotetrameric Core of Striatin- interacting Phosphatase and Kinase ( STRIPAK) Complex*[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(14):9651-9661. |
| APA | Chen, CC.,Shi, ZB.,Zhang, WQ.,Chen, M.,He, F.,...&Zhou, ZC.(2014).Striatins Contain a Noncanonical Coiled Coil That Binds Protein Phosphatase 2A A Subunit to Form a 2: 2 Heterotetrameric Core of Striatin- interacting Phosphatase and Kinase ( STRIPAK) Complex*.JOURNAL OF BIOLOGICAL CHEMISTRY,289(14),9651-9661. |
| MLA | Chen, CC,et al."Striatins Contain a Noncanonical Coiled Coil That Binds Protein Phosphatase 2A A Subunit to Form a 2: 2 Heterotetrameric Core of Striatin- interacting Phosphatase and Kinase ( STRIPAK) Complex*".JOURNAL OF BIOLOGICAL CHEMISTRY 289.14(2014):9651-9661. |
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