Role of chaperonins in protein folding. A new model of the GroEL/GroES complex architecture.

Polypeptide chain folds to native protein under physiological conditions. At least in vivo, in addition to physiological conditions, certain initial kinetic conditions are also required upon folding. These non-physiological conditions specify that amino acid residues of a polypeptide chain move to the folding place directionally beginning from the first N-terminal residue, sequentially one after another, and gradually one-by-one. Chaperonin complex provides in the cell for the initial kinetic requirements for co-translational folding of polypeptide chain to native protein in sites in the cytoplasm distant from the ribosome and in the plasma of organelles. A new model of the GroEL/GroES complex architecture is proposed using structural data on the GroEL and GroES chaperonins. The known models of the chaperonin complex structure suggest that it is formed by binding of a dome-like GroES oligomer to the end orifice of the GroEL cylinder via long mobile loops of its base. According to the new model, to form the complex two GroES oligomers one-by-one enter with their roofing, i.e., in an inverted way, into the GroEL cylinder and orifices and lock them. The proposed complex has the form of coaxial cylinders. It is sufficiently stable and cannot dissociate under physiological conditions. The complex becomes functionally active when it binds the incoming substrate polypeptide. An active GroEL/GroES complex resembles a hollow cylinder with end orifices. The diameter of the cavity and orifices is about 30 A.