ABSTRACT
Since the discovery and early characterization of the eukaryotic cytosolic chaperonin containing TCP-1 (CCT) in 1992 (Lewis et al., 1992; Gao et al., 1992; Yaffe et al., 1992; Frydman et al., 1992), we have reviewed developments in this field annually (Horwich and Willison, 1993; Willison and Kubota, 1994; Kubota, Hynes and Willison, 1995a; Willison and Horwich, 1996). In contrast to the huge efforts being expended on the structure and reaction mechanism of the GroEL chaperonin of E. coli, there is still surprisingly little work being conducted on CCT. This may be partially due to a
1. Introduction 2. The Component Parts of CCT 2.1. CCT Gene Family 2.2. CCT is a Group II Chaperonin 2.3. CCT Gene Linkage in Lower Eukaryotes 2.4. Co-chaperones of CCT 2.5. Polypeptide Binding Sites on CCT 3. CCT Mediated Folding 3.1. Spectrum of Substrates 3.2. Tubulin Folding 4. CCT Function 4.1. CCT Functional Cycle 4.2. Co-translational Folding 4.3. Cell Biology 5. Conclusions 6. Acknowledgments 7. References
widespread perception that CCT is merely the eukaryotic equivalent of GroEL and that they must be very similar protein machines, sharing reaction mechanisms and functions in assisting general protein folding. However, evidence is accumulating that CCT is different to GroEL in many respects, particularly in its substrate specificity and interaction with co-chaperones. A stumbling block to the study of CCT is the absence of a high resolution structure, without which we will be unable to understand the significance of its multi-subunit nature and why 8 separate genes evolved to encode the core complex. The purpose of this chapter is not to re-review the early literature on CCT, but to give an up-to-date opinion on the composition and genetic structure of CCT, its natural substrates and mechanism of action. If, as we suspect from present data, CCT is a sequence specific chaperonin for the actins and tubulins, it may be possible in the future to determine the structures of their folding intermediates trapped on CCT. If this experimental approach proves successful, it should provide insight into the general nature of chaperone action and inform us how some partially folded proteins are truly perceived in the eukaryotic cytosol.
