Prefoldin, a Chaperone that Delivers Unfolded Proteins to Cytosolic Chaperonin

TLDR

The study reports the discovery of prefoldin, a heterohexameric chaperone that captures unfolded actin, and identifies its homologs in archaea, suggesting a general role in chaperonin‑mediated folding. The authors identified prefoldin homologs in archaea possessing class II chaperonin, indicating a conserved folding mechanism. Prefoldin binds cytosolic chaperonin and transfers unfolded proteins, and loss of prefoldin in yeast mimics chaperonin mutants, impairing actin and tubulin cytoskeletons, while its activity promotes folding amid competing pathways.

Abstract

We describe the discovery of a heterohexameric chaperone protein, prefoldin, based on its ability to capture unfolded actin. Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it. Deletion of the gene encoding a prefoldin subunit in S. cerevisiae results in a phenotype similar to those found when c-cpn is mutated, namely impaired functions of the actin and tubulin-based cytoskeleton. Consistent with prefoldin having a general role in chaperonin-mediated folding, we identify homologs in archaea, which have a class II chaperonin but contain neither actin nor tubulin. We show that by directing target proteins to chaperonin, prefoldin promotes folding in an environment in which there are many competing pathways for nonnative proteins.