Figure 3. Domain architecture of Vac7 and Atg18.

Vac7 is found only in some fungi. Atg18 is similar to mammalian WIPI1 and WIPI2; however, it is not known if these WIPI proteins regulate PIKfyve. For Vac7, boundaries of each domain were determined using a combination of Jpred4 secondary structure prediction and ClustalW multiple sequence alignment. Vac7 contains a coiled-coil domain (80% certainty using COILS) and a transmembrane domain. Atg18, WIPI1, and WIPI4 domain boundaries were determined from ClustalW multiple sequence alignment with Hsv2—a related protein where high-resolution structures are available [31, 75, 76]. Seven WD40 blades are depicted in green. A hydrophobic lipid-associated region is highlighted in blue. Beige Atg18 Loop is a predicted unstructured region between beta sheet 2 and 3 of blade 4. WIPI2 (not depicted) is structurally similar to WIPI1 and both contain an unstructured C-terminal tail with 31% similarity to each other. WIPI3 (not depicted) is structurally similar to WIPI4. Residue pockets predicted to bind PI(3)P and PI(3,5)P₂ are highlighted for ATG18, WIPI1, and WIPI4. That these regions are conserved indicates that Atg18, WIPI1, WIPI4 as well as their paralogs likely interact with phospholipids in a similar manner. Black lines represent 100 amino acids.