Chaperonin

Chaperonins are a class of molecular chaperones that assist in the folding of proteins, especially newly synthesized or stress-denatured polypeptides. They work by providing an isolated folding chamber that prevents aggregation and facilitates attainment of the native conformation in an ATP-dependent cycle. By accelerating correct folding, chaperonins help maintain proteome integrity and cellular function.

Most well-studied chaperonins fall into two groups. Group I chaperonins are found in bacteria and in the organelles of eukaryotes, such as mitochondria and chloroplasts. They form two stacked, seven-subunit rings (a double ring) that create a central folding chamber. A separate co-chaperonin, GroES, binds to one ring to seal the chamber during folding. Group II chaperonins are present in archaea and in the cytosol of eukaryotic cells; they lack a separate co-chaperonin and instead possess built-in lid structures that close the chamber.

A canonical example is the bacterial GroEL–GroES system. GroEL is a tetradecamer composed of two seven-subunit rings; GroES is a heptameric cap. Substrates bind to the hydrophobic interior of the open GroEL ring. ATP binding induces conformational changes that promote GroES binding and chamber closure. After ATP hydrolysis, the folded or partially folded substrate is released into the cytosol, and the cycle can repeat.

Chaperonins are essential for viability in many organisms, assist folding of a broad range of proteins, and help prevent aggregation under stress. They also represent potential targets for antimicrobial strategies, given the reliance of bacteria on their chaperonin systems.