Structural determinants for phosphatidylinositol recognition by Sfh3 and substrate-induced dimer–monomer transition during lipid transfer cycles

• Yeast Sfh3 specifically binds to phosphatidylinositol.
• Un-liganded Sfh3 forms a dimer.
• Ligand binding dissociates Sfh3 dimers into monomers in a reversible manner.

Sec14 family homologs are the major yeast phosphatidylinositol/phosphatidylcholine transfer proteins regulating lipid metabolism and vesicle trafficking. The structure of Saccharomyces cerevisiae Sfh3 displays a conserved Sec14 scaffold and reveals determinants for the specific recognition of phosphatidylinositol ligand. Apo-Sfh3 forms a dimer through the hydrophobic interaction of gating helices. Binding of phosphatidylinositol leads to dissociation of the dimer into monomers in a reversible manner. This study suggests that the substrate induced dimer–monomer transformation is an essential part of lipid transfer cycles by Sfh3.

Structured summary of protein interactionsSfh3 and Sfh3bind by X-ray crystallography (View interaction)Sfh3 and Sfh3bind by molecular sieving (View interaction)