2006/01/17 by Peter C. Stirling, Jorge Cuéllar, Gabriel Alfaro +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · #Heat shock proteins research #Cellular Mechanics and Interactions #14-3-3 protein interactions #Tubulin #Ternary operation #Folding (DSP implementation) #Biophysics #Chemistry #Actin #Cell biology #Ternary complex #Microtubule #Biochemistry #Biology #Computer science #Engineering #Programming language
paper · pdf · doi:10.1074/jbc.m513235200
openalex publication_date 2006/01/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Many ATP-dependent molecular chaperones, including Hsp70, Hsp90, and the chaperonins GroEL/Hsp60, require cofactor proteins to regulate their ATPase activities and thus folding functions in vivo. One conspicuous exception has been the eukaryotic chaperonin CCT, for which no regulator of its ATPase activity, other than non-native substrate proteins, is known. We identify the evolutionarily conserved PhLP3 (phosducin-like protein 3) as a modulator of CCT function in vitro and in vivo. PhLP3 binds CCT, spanning the cylindrical chaperonin cavity and contacting at least two subunits. When present in a ternary complex with CCT and an actin or tubulin substrate, PhLP3 significantly diminishes the chaperonin ATPase activity, and accordingly, excess PhLP3 perturbs actin or tubulin folding in vitro. Most interestingly, however, the Saccharomyces cerevisiae PhLP3 homologue is required for proper actin and tubulin function. This cellular role of PhLP3 is most apparent in a strain that also lacks prefoldin, a chaperone that facilitates CCT-mediated actin and tubulin folding. We propose that the antagonistic actions of PhLP3 and prefoldin serve to modulate CCT activity and play a key role in establishing a functional cytoskeleton in vivo.