The biogenesis of proteins critically depends on the concurrent formation of peptide bonds and the folding of the nascent polypeptide chains as they emerge from ribosomes. In E. coli, the general nascent-chain binding molecular chaperones, trigger factor and DnaK (Hsp 70), cooperate to promote the proper folding of proteins, presumably by preventing non-productive intra and inter-molecular associations that would result in the misfolding and aggregation of the nascent chains in the crowded cellular environment. Additionally, some 10-15% of newly-synthesized proteins complete their folding in a sequestered environment provided by the GroEL chaperonin and its cofactor GroES.

In eukaryotes, Hsp70 also binds nascent chains, and a subset of proteins including actin and tubulins are known to depend on the cytosolic chaperonin TriC (also called CCT) for folding. Recently, a novel eukaryotic hetero-oligomeric protein complex termed GimC (prefoldin) has been shown to also play a role in the biogenesis of these cytoskeletal proteins. While the structures and functions of chaperonins and Hsp 70 proteins have been extensively characterized, comparatively little is known about the Gim complex.

Studies in yeast suggest that GmC is involved in the folding of actin in close cooperation with TriC, which does not rely on a GroES-like cofactor. Interestingly, Gim protein homologues are also found in archaea, where a chaperonin (thermosome) is also present but the otherwise ubiquitous Hsp70 system is found only in some organisms. Characterization of the archaeal Gim protein homologues is providing significant insight into the structures of the two related Gim complexes. Specifically, both archaeal and eukaryotic GimC are composed of two different classes of subunits that assemble into a hexameric complex. The archaeal Gim complex is a molecular chaperone capable of stabilizing a number of different non-native proteins, and releasing them to a chaperonin for folding to the native state, Thus, archaeal GimC may perform a role similar to Hsp70 during de novo protein folding in cooperation with the endogenous chaperonin.