GroELGroES

GroELGroES refers to the bacterial chaperonin system that assists in folding many cytosolic proteins in an energy-dependent manner. It consists of two major components: GroEL, a double-ring (two back-to-back seven-subunit rings) molecular machine forming a tetradecamer, and GroES, a single-ring seven-subunit co-chaperonin that acts as a cap. The structure creates an enclosed central chamber where substrate proteins can fold away from the crowded cytosol. GroES binds to one end of GroEL in an ATP-dependent manner, producing a sealed environment inside the cis chamber.

The GroEL–GroES system operates through an ATP-driven cycle. Substrates—often misfolded or newly synthesized polypeptides—bind to the apical domains of GroEL in the open, ATP-free state. ATP then binds to the equatorial domains, promoting a conformational change that allows GroES to cap the cis ring. The capped chamber provides an isolated, hydrophilic environment that can facilitate folding. After ATP hydrolysis, the substrate is released from the cis ring, and GroES dissociates, freeing the ring to reset. The cycle can involve alternating between the two rings, with the trans ring preparing to engage the next substrate while the cis ring undergoes resetting for another round.

GroELGroES is essential for the proper folding of a broad range of bacterial proteins and is highly conserved across bacteria. The operon encoding groEL and groES is heat-inducible, reflecting its role in the cellular heat-shock response. The system has been extensively studied as a model for ATP-dependent chaperone mechanics and has analogs in mitochondria (Hsp60 and Hsp10) that perform related functions in eukaryotes.