Fig 1.
Phylogenetic analysis of striatin-interacting phosphatase and kinase complex subunits across fungi and humans reveals deep evolutionary conservation.
The STRIPAK complex is composed of conserved subunits, including the scaffold A subunit (Tpd3/PP2AA), regulatory B subunit (Far8/STRN), and catalytic C subunit (Pph22/PP2AC) of protein phosphatase 2A (PP2A), along with several associated proteins: a striatin-interacting protein (Far11/STRIP), a tail-anchored membrane protein (Far9/SLMAP), a Phocein subfamily protein (Mob3), a small coiled-coil protein (SIKE), and a GCK family kinase (Stk24). To assess conservation across species, maximum likelihood phylogenies were constructed for each subunit with homologs identified in Homo sapiens and nine fungal species. These fungi include representatives from both the Ascomycota and Basidiomycota phyla, enabling comparisons across the major Dikarya clade of the fungal kingdom. A species-level phylogeny, based on established taxonomy, is shown for reference. Terminal nodes are colored according to percent sequence similarity to the human homolog. For the PP2A catalytic subunit, some species contain two paralogs (for example, Pph21 and Ppg1), both of which may participate in the STRIPAK complex. In some cases, multiple homologs have been identified for a given component, or the component was not found [21]. These patterns reflect both conservation and diversification of STRIPAK complex composition across eukaryotes. Trees were generated from trimmed MAFFT alignments using RAxML with the LG substitution model, 1,000 bootstrap replicates, and an extended majority-rule consensus approach. Bootstrap values >75 are indicated. Scale bars represent the number of amino acid substitutions per site.
Fig 2.
Structural model and functional roles of the fungal striatin-interacting phosphatase and kinase complex.
A schematic model illustrates the organization and interactions of conserved fungal STRIPAK subunits, based on AlphaFold-Multimer predictions and published literature [9,18]. The striatin subunit Far8 forms a homotetramer via coiled-coil domains (CC1–CC4), serving as a scaffold for complex assembly. The WD40 domains of Far8 extend outward to mediate substrate interactions. The membrane-anchored protein Far9 localizes the complex to organelle membranes, including the endoplasmic reticulum, mitochondria, and nuclear envelope. Additional interacting components, including the PP2A catalytic subunit (Pph22), scaffold subunit (Tpd3), STRIP homolog (Far11), Mob3, SIKE, and a GCK family kinase (Stk24), complete the core STRIPAK complex. STRIPAK carries out conserved functions across fungi, including regulation of sexual and asexual development, cell growth and proliferation, and virulence, by acting on key signaling pathways and substrates. Schematic was partially created with BioRender.com [38].