TY - CHAP

T1 - The TRiC/CCT Chaperonin and Its Role in Uncontrolled Proliferation

AU - Wang, Dan Yang

AU - Kamuda, Kamila

AU - Montoya, Guillermo

AU - Mesa, Pablo

PY - 2020

Y1 - 2020

N2 - 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 CCT alpha, beta, gamma, delta, epsilon, zeta, eta and theta 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.

AB - 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 CCT alpha, beta, gamma, delta, epsilon, zeta, eta and theta 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.

KW - Chaperonines

KW - Molecular machines

KW - Cell cycle

KW - Protein folding

KW - Allosterism

KW - ATP hydrolysis

KW - Protein-protein interaction

KW - X-ray

KW - cryoEM

KW - ANAPHASE-PROMOTING COMPLEX

KW - EUKARYOTIC CHAPERONIN

KW - MOLECULAR CHAPERONE

KW - CYTOPLASMIC CHAPERONIN

KW - CYTOSOLIC CHAPERONIN

KW - CCT CHAPERONIN

KW - SACCHAROMYCES-CEREVISIAE

KW - CONFORMATIONAL-CHANGES

KW - CRYSTAL-STRUCTURE

KW - LID CLOSURE

U2 - 10.1007/978-3-030-40204-4_2

DO - 10.1007/978-3-030-40204-4_2

M3 - Book chapter

C2 - 32297209

SN - 978-3-030-40203-7

T3 - Advances in Experimental Medicine and Biology

SP - 21

EP - 40

BT - HSF1 and Molecular Chaperones in Biology and Cancer

A2 - Mendillo, Marc Laurence

A2 - Pincus, David

A2 - ScherzShouval, Ruth

PB - Springer

ER -