Prefoldins

Abstract

Accurate folding is essential for the proper function of proteins. Prefoldin is one of the chaperoning factors that contribute to protein folding in archaea and eukaryotes. Although it still has maintained its heterohexameric jellyfish-like structure, it has undergone a progressive diversification throughout evolution, which has ended up with the appearance of the prefoldin-like complex. This evolutionary change parallels an increasing specificity for substrate recognition, from general binding to unfolded polypeptides in archaea to the highly specific recognition of certain substrates in eukaryotes. Prefoldin action on unfolded polypeptides contributes to its solubilisation in vitro, but acts mainly in vivo as a cochaperone, by transferring nascent polypeptides to class-II chaperonins. This role of prefoldin is particularly relevant in the assembly of actin filaments and microtubules. In addition to this function, prefoldins also play important roles in the assembly of other multimeric complexes, protein quality control, transcription factors regulation and chromatin dynamics.

Key Concepts

• Prefoldins are heterohexameric jellyfish-like complexes present in archaea and eukaryotes.
• Prefoldin acts as a cochaperone and facilitates the supply of unfolded or partially folded substrates to class II chaperonins.
• Archaeal prefoldin recognises a wide range of unfolded substrates, whereas eukaryotic prefoldin is highly specific.
• The best-known role of eukaryotic prefoldin is the cotranslational transfer of nascent actin and tubulin monomers to cytoplasmic class-II chaperonins for proper folding.
• Canonical prefoldin also plays functional roles related to gene expression and chromatin dynamics in the nucleus.
• The prefoldin-like complex exists only in eukaryotes and is involved in the assembly of multimeric protein complexes, such as nuclear RNA polymerases and phosphatidylinositol-3-kinase-related protein kinases like mTOR.