Figure 6. Model of TRiC hierarchical assembly and consequences of its dysregulation.

Co- or immediately post-translationally, CCT proteins from the negatively charged hemisphere assemble into subcomplexes and form a scaffold. CCT8 joins as a monomer, followed lastly by CCT1, CCT3, and CCT6, which are deterred from subcomplex formation amongst each other. Orphaned subunits and intermediates are rapidly degraded, and can form transient lower-order off-pathway associations with each other. This keeps the free energy landscape (B) broad, kinetically separating different holocomplexes and ensuring the cell can funnel subunits toward the proper pathway. Without ordered assembly, noncanonical holocomplexes can form with improper biochemical symmetry and aberrant function.