4N6J

Crystal structure of human Striatin-3 coiled coil domain

4N6J の概要

• エントリーDOI: 10.2210/pdb4n6j/pdb
• 分子名称: Striatin-3 (2 entities in total)
• 機能のキーワード: wd40, scaffolding protein, pp2a, ccm3, cam, cav, rassf., signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12313.23

構造登録者

Chen, C.,Shi, Z.,Zhou, Z. (登録日: 2013-10-13, 公開日: 2014-02-26, 最終更新日: 2024-11-06)

主引用文献

Chen, C.,Shi, Z.,Zhang, W.,Chen, M.,He, F.,Zhang, Z.,Wang, Y.,Feng, M.,Wang, W.,Zhao, Y.,Brown, J.H.,Jiao, S.,Zhou, Z.
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.Biol.Chem., 289:9651-9661, 2014

PubMed Abstract: 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.

PubMed: 24550388
DOI: 10.1074/jbc.M113.529297

実験手法

X-RAY DIFFRACTION (2.001 Å)