Structural insights into the the TRiC/CCT complex function and mechanism
Martes 25 de marzo
Aula 300, 12:00
"Structural insights into the the TRiC/CCT complex function and mechanism"
Guillermo Montoya
Abstract
CCT (chaperonin containing TCP-1, also know as TRiC) is a molecular machine that
forms a high molecular weight complex (1000 KDa). CCT has crucial relevance in several important
biological processes and 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, tubulin or actin). Therefore this complex is a possible
antitumoral target due to its regulation of crucial processes in cell division. 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. 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. The transition between the open and closed states is induced upon ATP
binding and hydrolysis, and triggers a complex set of intra- and inter-ring allosteric
- We successfully solved the structure of the open CCT complex including tubulin as a bound substrate at 5.5 Å
resolution. Using a hybrid approach we have suggested a new working model for this protein complex.