Predicted modeling of the PIKfyve complex, generation of a catalytic core construct of PIKfyve, and comparison with PPIn kinases. (A) Domain schematic of full-length H. sapiens PIKfyve and AlphaFold3 predicted structure of PIKfyve, Fig4, and the Vac14 pentamer with low-confidence regions (pLDDT <50) removed (Abramson et al., 2024) (see Fig. S1 for full modeling details). The ordered FYVE and DEP domains are omitted from the full-length PIKfyve structure because they are likely dynamic relative to the rest of the protein (see the PAE plot in Fig. S1). (B) AlphaFold3 predicted structure of the boxed region of PIKfyve from the schematic in A. (C) Comparison of the insert region in PI4P5Kα (PDB:4TZ7) with the linker between the CCR/CCT and 3HB domains of PIKfyve. (D) Domain schematic and AlphaFold3 predicted structure for the PIKfyve^CC with low-confidence regions (pLDDT <50) removed. Domains are colored to match the domain schematics in A. PAE, predicted aligned error.