Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation

Abstract

The chaperonin containing TCP-1 (CCT) is required for the production of native actin and tubulin and numerous other proteins, several of which are involved in cell cycle progression. The mechanistic details of how CCT acts upon its folding substrates are intriguing: whilst actin and tubulin bind in a sequence-specific manner, it is possible that some proteins could use CCT as a more general binding interface. Therefore, how CCT accommodates the folding requirements of its substrates, some of which are produced in a cell cycle-specific manner, is of great interest. The reliance of folding substrates upon CCT for the adoption of their native structures results in CCT activity having far-reaching implications for a vast array of cellular processes. For example, the dependency of the major cytoskeletal proteins actin and tubulin upon CCT results in CCT activity being linked to any cellular process that depends on the integrity of the microfilament and microtubule-based cytoskeletal systems.

Fig. 1

Subunit arrangement and three-dimensional analysis of CCT. (A) Cartoon diagram to illustrate the positioning of the eight CCT subunits within the chaperonin ring according to (Liou and Willison 1997). (B) Cryoelectron single-particle reconstruction of the CCT oligomer (Llorca et al 2001) and (C) CCT–actin complexes with actin binding to CCT in an open conformation spanning the chaperonin cavity (Llorca et al 1999). (D) Inter- and intra-ring arrangement of CCT subunits as determined by immunolabelling and cryoelectron single-particle microscopy (Martin-Benito et al 2007). Circular arrows show the direction of intra-ring sequential changes (Lin and Sherman 1997). Asterisks indicate subunits that may be involved in possible inter-ring signalling, with a basic signalling mechanism indicated by arrows (Martin-Benito et al 2007). (E) Comparison of the nomenclature of CCT subunits in mammals and yeast

Fig. 2

CCT coordinates an array of cellular functions via its folding substrates. CCT (shown here as a 3-dimensional reconstruction from single-particle electron microscopy, Llorca et al 2001) must be able to accommodate the folding of the major substrates actin and tubulin with additional substrates, some of which are required during cell cycle progression. Coloured arrows track the interactions of proteins with CCT