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TCP-1 (CCT)

Page updated 17/6/03

An actin chaperone that mediates folding of the nascent actin molecule.  The TCP-1 (T-complex polypeptide 1) is most often named the CCT for type II chaperonin containing T-complex (Kubota et al, 1994).  CCT is composed of 8 related, ~60kDa proteins that form a ring which then associates back-to-back to form a barrel-shaped structure (rev Valpuesta et al, 2002). There are indications that different complexes and individual subunits may performs functions also (Liou & Willison, 1997), and the complex may dissociate at cellular ATP and K levels (Roobol & Carden, 1999; Roobol et al, 1999). Some but not all of the CCT proteins bind actin and actin filaments (Grantham et al, 2002).  The net effect of the CCT complex on folded actin polymerization was to block polymerization at the barbed end (Grantham et al, 2002).
Subunit

 G-actin

 F-actin

References

 CCT a   ++  Co-sedimentation Grantham et al, 2002
         b +?  3D-reconstruction +       " Llorca et al, 1999;Grantham et al, 2002
         g   +       " Grantham et al, 2002
         d +    3D-reconstruction -        " Llorca et al, 1999;Grantham et al, 2002
         e +?  3D-reconstruction -+      " Llorca et al, 1999;Grantham et al, 2002
         x   ++     " Grantham et al, 2002
         h   +       " Grantham et al, 2002
         q   -+     " Grantham et al, 2002
       
Table 1    CCT complex and Actin-Binding
The binding sites of CCT on actin 

 

Cellular localization
CCT is localized to the leading edge of fibroblasts (
Roobol & Carden, 1999) and neurons (Roobol et al, 1995) where it may fold actin monomers as they are synthesised as actin mRNA is localised at the leading edge too (see). Barbed ends of actin filaments are generally abut the plasma membrane so it is possible that the barbed end binding of the CCT complex (Grantham et al, 2002) may be partially responsible. The CCT complex is transported with Hsc73 and actin in motor neurons (Bourke et al, 2002).
Carden Lab  University of Kent UK

References:-

Bourke, G. J., El Alami, W., Wilson, S. J., Yuan, A., Roobol, A. & Carden, M. J. (2002) Slow axonal transport of the cytosolic chaperonin CCT with Hsc73 and actin in motor neurons. J Neurosci Res. 68, 29-35.

Grantham, J., Ruddock, L. W., Roobol, A. & Carden, M. J. (2002) Eukaryotic chaperonin containing T-complex polypeptide 1 interacts with filamentous actin and reduces the initial rate of actin polymerization in vitro. Cell Stress & Chaperones. 7, 235-242.

Hansen, W. J., Cowan, N. J. & Welch, W. J. (1999) Prefoldin-Nascent Chain Complexes in the Folding of Cytoskeletal Proteins. J. Cell Biol. 145, 265-277.

Hynes, G. M. & Willison, K. R. (2000) Individual subunits of the eukaryotic cytosolic chaperonin mediate interactions with binding sites located on subdomains of b-actin. J.Biol.Chem. 275, 18985-18994.

Kubota, H., Hynes, G., Carne, A. Ashworth, A., &  Willison, K. R. (1994) Identification of six Tcp-1 related genes encoding divergent subunits of the TCP-1 containing chaperonin. Curr.Biol. 4, 89-99.

Kubota, H., Hynes, G. M., Kerr, S. M. & Willison, K. R. (1997) Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1. FEBS letters. 402, 53-56.

Liang, P. & MacRae, T. H. (1997) Molecular chaperones and the cytoskeleton. J.Cell Sci. 110, 14310-1440.

Liou, A.F.K. & Willison, K.R. (1997) Elucidation of the subunit orientation in CCT (Chaperonin containing TCP1) from the subunit composition of CCT micro-complexes. EMBO J 16, 4311-4316.

Llorca, O., McCormack, E. A., Hynes, G., Grantham, J., Cordell, J., Carrascosa, J. L., Willison, K. R., Fernandez, J. J. & Valpuesta, J. M. (1999) Eukaryotic type II chaperonin CCT interacts with actin through specific subunits. Nature. 402, 693-696.

Llorca, O., Martin-Benito, J., Ritco-Vonsovici, M., Grantham, J., Hynes, G. M., Willison, K. R., Carrascosa, J. L. & Valpuesta, J. M. (2000) Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations. EMBO J. 19, 5971-5979.

Llorca, O., Martin-Benito, J., Grantham, J., Ritco-Vonsovici, M., Willison, K. R., Carrascosa, J. L. & Valpuesta, J. M. (2001) The 'sequential allosteric ring' mechanism in the eukaryotic chaperonin-assisted folding of actin and tubulin, EMBO J. 20, 4065-4075.

Martin-Benito, J., Boskovic, J., Gomez-Puertas, P., Carrascosa, J. L., Simons, C. T., Lewis, S. A., Bartolini, F., Cowan, N. J. & Valpuesta, J. M. (2002) Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT. EMBO J. 21, 6377-6386.

McCormack, E. A., Llorca, O., Carrascosa, J. L., Valpuesta, J. M. & Willison, K. R. (2001) Point mutations in a hinge linking the small and large domains of beta-actin result in trapped folding intermediates bound to cytosolic chaperonin CCT., J Struct Biol. 135, 198-204.

McCormack, E. A., Rohman, M. J. & Willison, K. R. (2001) Mutational screen identifies critical amino acid residues of beta-actin mediating interaction between its folding intermediates and eukaryotic cytosolic chaperonin CCT. J Struct Biol. 135, 185-197.

Rommelaere, H., De Neve, M., Melki, R., Vanderkerkhove, J. & Ampe, C. (1999) The cytosolic class II chaperonin CCT recognizes delineated hydrophobic sequences in its targets proteins. Biochemistry. 38, 3246-3257.

Rommelaere, H., De Neve, M., Neirynck, K., Peelaers, D., Waterschoot, D., Goethals, M., Fraeyman, N., Vandekerckhove, J. & Ampe, C. (2001) Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families. J. Biol.Chem. 276, 41023-41028.

Roobol & Carden (1999) Subunits of the eukarotic cytosolic chaperonin CCT do not always behave as components of a uniform heterodimeric particle.  Eur.J.Cell Biol. 78,  21-32.

Roobol, A., Grantham, J., Whitaker, H. C. & Carden, M. J. (1999) Disassembly of the Cytosolic Chaperonin in Mammalian Cell Extracts at Intracellular Levels of K+ and ATP. J. Biol. Chem. 274, 19220-19227.

Valpuesta, J. M., Martin-Benito, J., Gomez-Puertas, P., Carrascosa, J. L. & Willison, K. R. (2002) Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett. 529, 11-16.

 
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