Chaperonins

Abstract The challenge in protein folding is the production of the native, active conformation from the primary sequence information. In vivo , in the cytosolic environment, acquisition of the native conformation is in competition with proteolytic degradation and/or intracellular precipitation. Chaperone proteins assist in finding the native fold in all cellular phases, and these key components of the cellular machinery occur ubiquitously through archaea, bacteria and eukarya. Chaperonins are complex polymeric proteins that form a closed environment, the ‘Anfinsen cage’, to allow correct protein folding triggered by adenosine triphosphate hydrolysis, avoiding intermolecular aspecific aggregation. The chaperonins prevent protein unfolding and misfolding, events responsible for several human diseases, such as cancer and amyloid diseases. The chaperonins are considered potential drug targets due to their role in protein misfolding, aggregation and denaturation and in cellular signalling. Key Concepts: Proteins must fold properly to acquire their native and functional conformation. Protein misfolding is characterised by the exposure of buried hydrophobic residues. Protein misfolding may be followed by protein aggregation. The folding of many proteins need to be assisted by other proteins to prevent misfolding and/or aggregation. The chaperonins prevent protein unfolding and misfolding, events responsible for several human diseases, such as cancer and amyloid diseases. The ‘Anfinsen cage’ is a closed environment that encapsulates the nonnative protein and allows correct protein folding in the internal chaperonin compartment.