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
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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.
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Striatin family members share a coiled-coil domain, a caveolin-binding domain, and a calmodulin-binding domain in the N-terminus, plus a C-terminal WD40 repeat domain.
“The three Striatin family members share four conserved domains: a coiled coil domain, a caveolin-binding domain, and a calmodulin-binding domain within the N-terminus; and a WD40 repeat domain within the C-terminus (Chen et al., 2014; Moreno et al., 2000).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Chen et al., 2014
SG2NA homodimerization is required for its interaction with PP2A and for STRIPAK assembly.
“Mutational studies have revealed that SG2NA homodimerization is required for its interaction with PP2A and thus the assembly of STRIPAK complexes (Chen et al., 2014).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Chen et al., 2014
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- Authors
- 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.
- Affiliations
- Chinese Academy of Sciences (CN)
- Tongji University (CN)
- Brandeis University (US)
- Corresponding author
- Jiao, Shi
- Zhou, Zhaocai
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 289
- Issue
- 14
- Pages
- 9651-9661
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3975014
- OpenAlex
- W2001469017
- Cited by
- 47
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- STRIPAK complex, protein phosphatase 2A, coiled-coil domain, crystal structure, MST3, MO25, CCM3, homodimerization, apoptosis, kinase regulation
- MeSH terms
- Germinal Center Kinases, Hippo Kinases, Autoantigens, Calmodulin-Binding Proteins, Humans, Nerve Tissue Proteins, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Crystallography, X-Ray, Jurkat Cells, Protein Structure, Quaternary, Multiprotein Complexes, Protein Phosphatase 2
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