Chaperonin: Protein Folding Machinery in Cells

Abstract

As ribosomes initiate synthesis of a polypeptide chain, its precise folding into the functional three-dimensional protein structure is achieved either by spontaneous self-folding or by chaperonin-assisted folding requiring ATP. Spontaneous self-folding is achieved and dictated by its linear amino acid sequence and the existing intracellular environment (such as pH and temperature of the nano environment) to be thermodynamically favorable to assume a negative Gibbs free energy value. In contrast, chaperonin assists folding by preventing incorrect folding conformations and aggregation. Chaperonins are double ring structures stacked one over the other to form a protein-folding chamber in the center of the stack. In E. coli, the protein-folding chaperone machinery measures 18.4 nm in length and 14 nm wide and is comprised of two rings stacked one over the other, with each ring composed of seven subunits. Each subunit is composed of three domains, including an ATP-binding domain. The binding of ATP leads to the establishment of a hydrophilic cage for protein folding. Mutations in genes encoding chaperones, or changes in the expression levels of chaperones, have been identified to result in a wide range of disorders.