ABSTRACT
Protein folding effi ciency is enhanced in vivo by an array of chaperones and folding-assisting enzymes that cover the entire protein folding pathway, from the exit of the polypeptide from the ribosome, its translocation through membranes, disulfi de bond formation, tertiary structure acquisition, and oligomer assembly. A protein acquires diverse conformational states during these processes, from extended and disordered structures when exiting the ribosome to more structured intermediates such as molten globule-like forms. Accordingly, the high diversity of chaperones refl ects the conformational variety of their substrates. From a statistical point of view, the native state represents an extremely small fraction of the conformational space available to a protein, which may easily fall into irreversible kinetic traps during the folding process. In this sense, the crowded environment inside a cell represents a hostile scenario for protein folding, where protein aggregation could be the rule rather than the exception. One of the main functions of chaperones, perhaps the most important, is to inhibit nonspecifi c protein interactions, directing the protein to a productive folding pathway.
