Chaperonins – Discovery of the Machines and their Action in Assisting Protein Folding to the Native State

Chaperonin machines are large ring assemblies that mediate ATP-dependent protein folding to the native state by binding and folding proteins in the cavities of their rings. They are present in the cytosol of organisms from all three kingdoms of life and are present also in chloroplasts and mitochondria, Eukaryotic organelles that are endosymbiotically related to Eubacteria. Their biological action in assisting protein folding is essential – deletion of these components is lethal.

The possibility of a protein “folding machine” was entertained by Anfinsen and coworkers as early as 1963 (Epstein et al., 1963) and subsequently considered by others (e.g., Rothman and Kornberg, 1986). The course of experiments that demonstrated such a component was not a linear one, however. In the early 1970s, a role was identified for a Bacterial operon known as groE in enabling productive phage infection of Bacteria. In particular, genetic deficiency in this locus led to an accumulation of aggregated phage head “monsters” inside infected E. coli, suggesting a role for this operon in phage particle assembly (Georgopoulos et al., 1972; Takano and Kakefuda, 1972). A broader role, however, in cellular metabolism was suggested by the observation that groE mutant cells grew poorly even in the absence of phage infection. In the late 1970s, electron microscopy studies of a purified product of the groE operon, the “large” component called GroEL, revealed a remarkable double-ring architecture, with rings composed of seven identical subunits surrounding a central “hole” (Hendrix, 1979; Hohn et al., 1979).