TRiC

TRiC, also known as the TCP-1 Ring Complex or chaperonin-containing TCP-1, is a cytosolic chaperonin complex in eukaryotes. It functions as a double-ring assembly, with two stacked rings each composed of eight distinct subunits (CCT1–CCT8). The complex forms a large central chamber that provides an isolated environment for folding polypeptides, and its activity is ATP-dependent.

The eight different subunits combine to form a single, hetero-oligomeric complex. Each subunit contains a nucleotide-binding domain, and ATP binding and hydrolysis drive conformational changes that regulate substrate encapsulation, folding, and release. The precise arrangement of subunits contributes to substrate specificity and efficiency of folding for different client proteins.

TRiC assists the folding of a subset of cytosolic proteins, most notably actin and tubulin, which are essential for the cytoskeleton. It also helps fold various other proteins, including certain kinases and transcription factors. In cellular folding pathways, prefoldin can deliver nascent substrates to TRiC, after which ATP-driven conformational cycles within the chamber promote correct folding and eventual release of mature proteins.

Mechanistically, TRiC is a group II chaperonin. Unlike GroEL/GroES, it lacks a detachable lid; instead, built-in apical domains form a cap that closes the chamber upon ATP binding and hydrolysis. The complex is essential for cell viability and proper cytoskeletal organization and is broadly conserved across eukaryotes.

Clinical and research notes indicate that TRiC activity influences protein homeostasis and may be involved in aging and disease processes. It remains a focus of study for understanding chaperone networks and exploring therapeutic implications in cancer and neurodegenerative disorders.