Molecular mechanisms of chaperonin GroEL-GroES function

Abstract

The dynamics of the GroEL-GroES complex is investigated with a coarse-grained model. This model is one in which single-residue points are connected to other such points, which are nearby, by identical springs, forming a network of interactions. The nature of the most important (slowest) normal modes reveals a wide variety of motions uniquely dependent upon the central cavity of the structure, including opposed torsional rotation of the two GroEL rings accompanied by the alternating compression and expansion of the GroES cap binding region, bending, shear, opposed radial breathing of the cis and trans rings, and stretching and contraction along the protein assembly's long axis. The intermediate domains of the subunits are bifunctional due to the presence of two hinges, which are alternatively activated or frozen by an ATP-dependent mechanism. ATP binding stabilizes a relatively open conformation (with respect to the central cavity) and hinders the motion of the hinge site connecting the intermediate and equatorial domains, while enhancing the flexibility of the second hinge that sets in motion the apical domains. The relative flexibilities of the hinges are reversed in the nucleotide-free form. Cooperative cross-correlations between subunits provide information about the mechanism of action of the protein. The mechanical motions driven by the different modes provide variable binding surfaces and variable sized cavities in the interior to enable accommodation of a broad range of protein substrates. These modes of motion could be used to manipulate the substrate's conformations.