Å. Some bacteria use multiple copies of this chaperonin, probably for different peptides. Group II Group II chaperonins (TCP-1), found in the eukaryotic cytosol and in archaea, are more poorly characterized. The complex in archaea is called the thermosome. A homo-16mer in some archaea, it is regarded as the prototypical type II chaperonin. TRiC, the eukaryotic chaperonin, is composed of two rings of eight different though related subunits, each thought to be represented once per eight-membered ring. TRiC was originally thought to fold only the cytoskeletal proteins actin and tubulin but is now known to fold dozens of substrates. Methanococcus maripaludis chaperonin (Mm cpn) is composed of sixteen identical subunits (eight per ring). It has been shown to fold the mitochondrial protein rhodanese; however, no natural substrates have yet been identified. Group II chaperonins are not thought to utilize a GroES-type cofactor to fold their substrates. They instead contain a "built-in" lid that closes in an ATP-dependent manner to encapsulate its substrates, a process that is required for optimal protein folding activity. They also interact with a co-chaperone, prefoldin, that helps move the substrate in. Other families Group III includes some bacterial Cpns that are related to Group II. They have a lid, but the lid opening is noncooperative in them. They are thought to be an ancient relative of Group II. A Group I chaperonin gp146 from phage EL does not use a lid, and its donut interface is more similar to Group II. It might represent another ancient type of chaperonin. Mechanism of action Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatic hydrolysis of ATP as well as binding of substrate proteins and cochaperonins, such as GroES. These conformational changes allow the chaperonin to bind an unfolded or misfolded protein, encapsulate that protein within one of the cavities formed by the two rings, and release the protein back into solution. Upon release, the substrate protein will either be folded or will require further rounds of folding, in which case it can again be bound by a chaperonin. The exact mechanism by which chaperonins facilitate folding of substrate proteins is unknown. According to recent analyses by different experimental techniques, GroEL-bound substrate proteins populate an ensemble of compact and locally expanded states that lack stable tertiary interactions. A number of models of chaperonin action have been proposed, which generally focus on two (not