Novel Binding Partners for CCT and PhLP1 Suggest a Common Folding Mechanism for WD40 Proteins with a 7-Bladed Beta-Propeller Structure

This study investigates whether selected WD40 proteins with a 7-bladed beta-propeller structure, similar to that of the beta subunit of the G protein heterotrimer, interact with the cytosolic chaperonin CCT and its known binding partner, PhLP1. Previous studies have shown that CCT is required for the folding of the G beta subunit and other WD40 proteins. The role of PhLP1 in the folding of G beta has also been established, but it is unknown if PhLP1 assists in the folding of other G beta-like proteins. The binding of three G beta-like proteins, TBL2, MLST8 and CDC20, to CCT and PhLP1, was demonstrated in this study. Co-immunoprecipitation assays identified one novel binding partner for CCT and three new interactors for PhLP1. All three of the studied proteins interact with CCT and PhLP1, suggesting that these proteins may have a folding machinery in common with that of G beta and that the well-established G beta folding mechanism may have significantly broader biological implications than previously thought. These findings contribute to continuous efforts to determine common traits and unique differences in the folding mechanism of the WD40 beta-propeller protein family, and the role PhLP1 has in this process.