GroEL

GroEL is a bacterial chaperonin that, together with its co-chaperonin GroES, forms a folding machine essential for the proper biogenesis of many cytosolic proteins. It assists protein folding, especially under heat shock and other stress conditions, by preventing aggregation and promoting correct folding.

GroEL is a ~57-60 kDa polypeptide that assembles into a tetradecamer, consisting of two back-to-back, seven-subunit rings. Each ring contains three major domains: an equatorial domain that binds ATP and mediates intersubunit contacts, an apical domain that recognizes substrate proteins, and an intermediate domain that connects the other two. GroES is a small, seven-subunit co-chaperonin that binds to the apical domains of GroEL in the presence of ATP, effectively capping one ring and creating a secluded folding chamber.

Folding proceeds via an ATP-dependent cycle. A substrate polypeptide binds to the apical domains of the cis GroEL ring. Binding of ATP and association of the GroES cap encloses the substrate within a hydrophilic central cavity, isolating it from the cytosol. After ATP hydrolysis and GroES release, the folded or partially folded protein is released, and the cycle can reinitiate with another polypeptide, either in the same ring or in the opposite ring.

GroEL is encoded by the groEL gene and is often co-transcribed with groES in the groEL/groES operon. It is essential in many bacteria and is a key component of the cellular heat shock response. Homologous systems exist in mitochondria and chloroplasts (Hsp60) and in eukaryotes as the chaperonin TRiC/CCT complex, reflecting a conserved mechanism for assisting the proper folding of a wide range of proteins.