Chaperonin-mediated folding of actin and tubulin.

Abstract

T HE central dogma of molecular biology holds that proteins contain within their primary amino acid sequence all the information that is required to dictate their three-dimensional structure. In principle, therefore, proteins can fold spontaneously (2). It is now clear, however, that the proper folding of many proteins requires facilitation. The facilitation reaction is accomplished via interaction with chaperonins, a class of multisubunit toroidal complexes which hydrolyzes ATP as part of the mechanism whereby its members contribute to the productive folding of their target polypeptides (4, 5, 11, 12, 15, 16, 20). Chaperonins are both structurally and functionally distinct from a class of molecules (typified by the heat shock protein hsp70) that is also thought to participate in the overall protein folding pathway by maintaining polypeptides in a partially unfolded conformation pending their translocation or presentation to chaperonin (for a review see reference 15). Bacteria, chloroplasts, mitochondria, and the cytosol of eukaryotes each contain a single kind of chaperonin molecule. These are different from one other, but homologous. No chaperonin has so far been found in the endoplasmic reticulum. Here we present our view of how the eukaryotic cytosolic chaperonin functions, particularly in relation to what is known about the mechanism of facilitated folding by chaperonin from prokaryotes.