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The TRiC/CCT Chaperonin and Its Role in Uncontrolled Proliferation

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HSF1 and Molecular Chaperones in Biology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1243))

Abstract

The cell cycle is a sophisticated space-time regulated mechanism where a wide variety of protein modules and complexes associate functioning in a concerted manner to regulate and transfer the genetic material to daughter cells. CCT (chaperonin containing TCP-1, also known as TRiC) is a molecular machine that forms a high molecular weight complex (1000 KDa). CCT is emerging as a key molecule during mitosis due to its essential role in the folding of many important proteins involved in cell division (Cdh1, Plk1, p27, Cdc20, PP2a regulatory subunits, tubulin or actin) suggesting its involvement in uncontrolled proliferation. The assembly is formed by eight different subunits called CCTα, β, γ, δ, ε, ζ, η and θ in mammals corresponding to CCT1–8 in yeast. CCT/TRiC is organized in a unique intra- and inter-ring arrangement. The chaperonin monomers share a common domain structure including an equatorial domain, which contains all the inter-ring contacts, most of the intra-ring contacts and the ATP binding site, whose binding and hydrolysis triggers the conformational changes that take place during the functional cycle. All chaperonins display an open substrate-receptive conformation, where the unfolded protein is recognized and trapped, and a closed conformation where the substrate is isolated from the bulk of the intracellular environment. In this chapter we discuss the complex set of intra- and inter-ring allosteric signals during chaperonin function.

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Acknowledgements

The Novo Nordisk Foundation Center for Protein Research is supported financially by the Novo Nordisk Foundation (Grant NNF14CC0001). This work was also supported by the cryoEM (Grant NNF0024386) and cryoNET (Grant NNF17SA0030214) grants to GM, Guillermo Montoya is a member of the Integrative Structural Biology Cluster (ISBUC) at the University of Copenhagen.

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Authors and Affiliations

  1. Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Dan Yang Wang, Kamila Kamuda, Guillermo Montoya & Pablo Mesa

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  1. Dan Yang Wang
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  2. Kamila Kamuda
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  3. Guillermo Montoya
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  4. Pablo Mesa
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Correspondence to Guillermo Montoya .

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Editors and Affiliations

  1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Marc Laurence Mendillo

  2. University of Chicago, Chicago, IL, USA

    David Pincus

  3. Weizmann Institute of Science, Rehovot, Israel

    Ruth Scherz-Shouval

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Wang, D.Y., Kamuda, K., Montoya, G., Mesa, P. (2020). The TRiC/CCT Chaperonin and Its Role in Uncontrolled Proliferation. In: Mendillo, M.L., Pincus, D., Scherz-Shouval, R. (eds) HSF1 and Molecular Chaperones in Biology and Cancer. Advances in Experimental Medicine and Biology, vol 1243. Springer, Cham. https://doi.org/10.1007/978-3-030-40204-4_2

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