Assembly reactions chaperone proteins

In vivo, the correct assembly of proteins is guided by a family of cellular proteins termed molecular chaperones, e.g., heat shock protein (HSP), nuleoplasmins, and chaperonins. Chaperones bind to the intermediate that tends to aggregate, and either assembles the intermediate to the native state or renders the intermediate void of further reaction to form an aggregate. Normally, all proteins should fold without molecular chaperones. Proteins that tend to form aggregates, like those shown in the above mechanisms, bind to a chaperone to yield the native state. 

These mechanisms are not mutually exclusive. Many examples of metallocenter synthesis utilize multiple mechanisms. In addition, it is important to note that metallocenter assembly can be driven by nucleotide hydrolysis reactions, typically involving mechanism 7. L, protein ligand L, covalently modified ligand X, non-metal component of a metallocenter Y, component required for the synthesis of a metal-containing cofactor C, molecular chaperone. 

The principal targets for facilitated folding by CCT in cooperation with prefoldin are the cytoskeletal proteins actin and tubulin. The actin monomer assembles into microfilaments, while the subunit that forms microtubules is the tubulin heterodimer, which consists of a single a- and a single /f-tubulin polypeptide. Though actin can be folded to the native state via one or more cycles of ATP-dependent interaction with CCT, this is not the case for either a- or /Ttubulin. Tubulin subunits released from CCT are assembled into a/fi heterodimers by interaction with several tubulin-specific chaperones known as cofactors in a reaction that depends on GTP hydrolysis by the cofactor-bound tubulin. 

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