12 The Structure, Function, and Genetics of the Chaperonin Containing TCP-1 (CCT) in Eukaryotic Cytosol

Abstract

I. INTRODUCTION
The double-torus chaperonins are one class of molecular chaperones found in eubacteria, mitochondria, and plastids that bind protein substrates at some intermediate stage in their protein folding pathways and use ATP hydrolysis to fold and release them as biologically active, correctly folded products (Horwich and Willison 1993; Saibil and Wood 1993; see Frydman and Hartl, this volume).

Recently, it has become clear that eukaryotic cytosol contains an abundant ring-shaped chaperonin that is composed of many kinds of subunits encoded by a family of related genes. The discovery of the cytosolic chaperonin containing TCP-1 (CCT) arose from the convergence of three independent lines of investigation. First, our laboratory had been investigating the mouse t-complex polypeptide 1 (Tcp-1) gene that maps to the t-complex region of mouse chromosome 17 (Silver et al. 1979) and is up-regulated during spermatogenesis (Dudley et al. 1984; Silver et al. 1987; Willison et al. 1990). We cloned mouse Tcp-1 (Willison et al. 1986; Kubota et al. 1992b) and human TCP1 (Willison et al. 1987; Kirchoff and Willison 1990) cDNAs and genes, made a set of seven monoclonal antibodies to the protein (Willison et al. 1989), and biochemically purified the chaperonin containing TCP-1 (Lewis et al. 1992). Second, investigation of the heat shock response in two species of thermophilic archaebacteria uncovered a novel, heat-inducible, double-toroid ATPase with in vitro chaperonin activity (Phipps et al. 1991Phipps et al. 1993; Trent et al. 1991). The subunits of these archaebacterial chaperonins are highly related to eukaryotic TCP-1, 40% identical in the...