Folding in vivo of bacterial cytoplasmic proteins: role of GroEL.

A general role for chaperonin ring structures in mediating folding of newly translated proteins has been suggested. Here we have directly examined the role of the E. coli chaperonin GroEL in the bacterial cytoplasm by production of temperature-sensitive lethal mutations in this essential gene. After shift to nonpermissive temperature, the rate of general translation in the mutant cells was reduced, but, more specifically, a defined group of cytoplasmic proteins--including citrate synthase, ketoglutarate dehydrogenase, and polynucleotide phosphorylase--were translated but failed to reach native form. Similarly, a monomeric test protein, maltose-binding protein, devoid of its signal domain, was translated but failed to fold to its native conformation. We conclude that GroEL indeed is a machine at the distal end of the pathway of transfer of genetic information, assisting a large and specific set of newly translated cytoplasmic proteins to reach their native tertiary structures.