Chaperonins are large ring assemblies that assist protein folding to the native 
state by binding nonnative proteins in their central cavities and then, upon 
binding ATP, release the substrate protein into a now-encapsulated cavity to 
fold productively. Two families of such components have been identified: type I 
in mitochondria, chloroplasts, and the bacterial cytosol, which rely on a 
detachable "lid" structure for encapsulation, and type II in archaea and the 
eukaryotic cytosol, which contain a built-in protrusion structure. We discuss 
here a number of issues under current study. What is the range of substrates 
acted on by the two classes of chaperonin, in particular by GroEL in the 
bacterial cytoplasm and CCT in the eukaryotic cytosol, and are all these 
substrates subject to encapsulation? What are the determinants for substrate 
binding by the type II chaperonins? And is the encapsulated chaperonin cavity a 
passive container that prevents aggregation, or could it be playing an active 
role in polypeptide folding?