The primary amino acid sequence of a protein contains all the information necessary for protein folding and its biological activity [1
]. However, in a normal cellular condition, a nascent polypeptide chain faces a crowded environment and there is a good possibility that protein will be misfolded and will form aggregates that make the protein inactive, and in certain cases it becomes toxic for the cell. Both the prokaryotic and eukaryotic cells possess a family of proteins responsible for binding to nascent polypeptide chains and help them fold into biologically functional three-dimensional structures, they are known as molecular chaperones, and they vary in size and complexity [2
]. Many of the molecular chaperones are induced in response to stress or heat, and so they got the name Hsp (heat shock protein). Molecular chaperones like Hsp90, Hsp70, Hsp40, and Hsp104 bind to nascent polypeptide chain at hydrophobic regions which are exposed to the crowded environment otherwise buried inside in a completely folded protein [7
]. Molecular chaperones have developed multiple and diverse tertiary and quaternary structures to bind nonnative protein substrates. Though, there is a lack of sequence similarity among different families of chaperones and only a few of them are represented in all three domains of life (bacteria, archaea, and eukaryote), generally, they use convergent strategies to bind the substrates. Crystallographic and other evidence show that many chaperones including prefoldin, trigger factor, hsp40, and hsp90 have clamp-like structures, possibly responsible for the binding of nonnative substrates [11
]. Another class of cylindrical-shaped chaperones, known as chaperonins, is found to be conserved in all three domains of life and assist the folding of many cytosolic proteins [12
]. In some cases, the transient binding of nascent polypeptide chain is sufficient for protecting its hydrophobic regions and promoting its proper folding. However, for the folding of a multidomain protein, more than one class of chaperones might be involved, and they work in a concerted manner to generate a protective passage. For example, nascent polypeptide chain coming out from ribosome will first bind to Hsp70/Hsp90 which will help attain a quasinative structure and then will be transferred to chaperonin CCT for its final folding [14
]. Here we review the current status of understanding of protein folding by the chaperonin CCT complex in eukaryotes.
The chaperonins are large, multimeric, cylindrical protein complexes consisting of two stacked rings and each ring has 7–9 subunits [2
]. On the basis of amino acid sequence homology, chaperonins have been categorized into two groups, group I and group II [19
]. Group I is found in all eubacteria and endosymbiotic organelles like mitochondria, chloroplasts, and related organelles like hydrogenosomes and mitosomes whereas group II chaperonins are present in archaebacteria and in the cytosol of all eukaryotes [2
]. Here we will give brief introduction to group I chaperonin and then will discuss group II chaperonin, CCT.