prefoldin

Prefoldin is a molecular chaperone complex that acts as a cochaperone for the cytosolic chaperonin CCT (also known as TRiC) and helps deliver unfolded or nascent polypeptides to the folding machinery in the cytosol. By binding non-native proteins, prefoldin prevents aggregation and facilitates productive interactions with the main chaperonin complex.

In eukaryotes, prefoldin is a heterohexamer composed of six different subunits, typically labeled PFDN1 through PFDN6. In archaea, homologous complexes exist as well, reflecting an evolutionarily conserved mechanism for assisting protein folding. Structurally, prefoldin has a jellyfish-like architecture with a central body formed by coiled-coil helices and long tentacle-like extensions that extend away from the core. The tentacles capture substrate proteins and present them to the chaperonin.

Mechanistically, prefoldin binds unfolded polypeptides as they emerge from ribosomes or arise from misfolded conformations. The bound clients are then transferred to the CCT/TRiC chamber, where the proteins undergo proper folding in an ATP-dependent cycle. Prefoldin often acts early in the folding pathway, helping to stabilize substrates until they can be folded within the chaperonin complex.

Biologically, prefoldin contributes to proteostasis and is particularly important for the biogenesis of cytoskeletal components such as actin and tubulin. It is primarily cytosolic and is conserved across archaea and eukaryotes, whereas bacteria generally lack prefoldin. Structural and biochemical studies have clarified its elongated, tentacled architecture and its role as a substrate delivery module to CCT/TRiC.