  Chaperonins are biological nanomachines that help newly translated proteins
to fold by rescuing them from kinetically trapped misfolded states. Protein
folding assistance by the chaperonin machinery is obligatory in vivo for a
subset of proteins in the bacterial proteome. Chaperonins are large oligomeric
complexes, with unusual seven fold symmetry (group I) or eight/nine fold
symmetry (group II), that form double-ring constructs, enclosing a central
folding chamber. Dramatic large-scale conformational changes, that take place
during ATP-driven cycles, allow chaperonins to bind misfolded proteins,
encapsulate them into the expanded cavity and release them back into the
cellular environment, regardless of whether they are folded or not. The theory
associated with the iterative annealing mechanism, which incorporated the
conformational free energy landscape description of protein folding,
\textit{quantitatively} explains most, if not all, the available data.
Misfolded conformations are associated with low energy minima in a rugged
energy landscape. Random disruptions of these low energy conformations result
in higher free energy, less folded, conformations that can stochastically
partition into the native state. Group I chaperonins (GroEL homologues in
eubacteria and endosymbiotic organelles), recognize a large number of misfolded
proteins non-specifically and operate through highly coordinated cooperative
motions. By contrast, the less well understood group II chaperonins (CCT in
Eukarya and thermosome/TF55 in Archaea), assist a selected set of substrate
proteins. Chaperonins are implicated in bacterial infection, autoimmune
disease, as well as protein aggregation and degradation diseases. Understanding
the chaperonin mechanism and their substrates is important not only for the
fundamental aspect of cellular protein folding, but also for effective
therapeutic strategies.
