Received July 3, 1997
The chaperonin system GroEL/GroES assists in the folding of proteins in the bacterial cytosol. Recent applications of biophysical techniques for the structural analysis of GroEL, GroES, and chaperonin-bound protein folding intermediates have provided the basis for understanding the molecular mechanism of GroEL/GroES action. GroEL, a double-ring complex, binds unfolded proteins at its inner ring surface. Protein folding proceeds in the central cavity of GroEL, after dissociation of the polypeptide has been triggered by ATP hydrolysis in GroEL. Premature release of unfolded protein into external solution is prevented by binding of the cofactor GroES on top of the GroEL cylinder, resulting in an enclosed cage. Upon ATP-dependent dissociation of GroES, substrate protein is eventually released from GroEL in a native or native-like conformation. While current in vitro results about the structure, function, and molecular mechanism of GroEL/GroES-assisted protein folding have led to a quite detailed picture of this complex process, the extent to which the GroEL/GroES system actually participates in the folding of newly-synthesized proteins in the cell is less defined and remains a subject for further studies. Ingenious biochemical and genetic approaches will be necessary to show whether our current view of chaperonin action indeed accurately reflects its modus operandi inside a living cell.
KEY WORDS: protein folding, molecular chaperone, chaperonin, GroEL, GroES