Molecular chaperones promote the correct folding of proteins in 
aggregation-prone cellular environments by stabilizing nascent polypeptide 
chains and providing appropriate folding conditions. Prefoldins (PFDs) are 
molecular chaperones found in archaea and eukaryotes, generally characterized by 
a unique jellyfish-like hexameric structure consisting of a rigid beta-barrel 
backbone with protruding flexible coiled-coils. Unlike eukaryotic PFDs that 
mainly interact with cytoskeletal components, archaeal PFDs can stabilize a wide 
range of substrates; such versatility reflects PFD's role as a key element in 
archaeal chaperone systems, which often lack general nascent-chain binding 
chaperone components such as Hsp70. While archaeal PFDs mainly exist as 
hexameric complexes, their structural diversity ranges from tetramers to 
filamentous oligomers. PFDs bind and stabilize nonnative proteins using varying 
numbers of coiled-coils, and subsequently transfer the substrate to a group II 
chaperonin (CPN) for refolding. The distinct structure and specific function of 
archaeal PFDs have been exploited for a broad range of applications in 
biotechnology; furthermore, a filament-forming variant of PFD has been used to 
fabricate nanoscale architectures of defined shapes, demonstrating archaeal 
PFDs' potential applicability in nanotechnology.