T-complex protein Ring Complex (TRiC), otherwise known as Chaperonin Containing TCP-1 (CCT), [lower-alpha 1] is a multiprotein complex and the chaperonin of eukaryotic cells. Like the bacterial GroEL, the TRiC complex aids in the folding of ~10% of the proteome, and actin and tubulin are some of its best known substrates. [2] [3] TRiC is an example of a biological machine that folds substrates within the central cavity of its barrel-like assembly using the energy from ATP hydrolysis.
The human TRiC complex is formed by two rings containing 8 similar but non-identical subunits, each with molecular weights of ~60 kDa. The two rings are stacked in an asymmetrical fashion, forming a barrel-like structure with a molecular weight of ~1 MDa. [2] [3]
| Subunit | MW (kDa) [A] | Features |
|---|---|---|
| TCP1 (CCT1/α) | 60 | |
| CCT2 (β) | 57 | |
| CCT3 (γ) | 61 | |
| CCT4 (δ) | 58 | |
| CCT5 (ε) | 60 | |
| CCT6 (ζ) | 58 | Two copies in human genome, CCT6A and CCT6B. |
| CCT7 (η) | 59 | |
| CCT8 (θ) | 60 | |
A Molecular weight of human subunits.
Counterclockwise from the exterior, each ring is made of the subunits in the following order: 6-8-7-5-2-4-1-3. [4]
 | This section is missing information about phylogeny (template) and evolutionary trajectory (pic).(December 2020) |
The CCT evolved from the archaeal thermosome ~2Gya, with the two subunits diversifying into multiple units. The CCT changed from having one type of subunit, to having two, three, five, and finally eight types. [4] : fig. 4
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm.
GroEL is a protein which belongs to the chaperonin family of molecular chaperones, and is found in many bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES. In eukaryotes the organellar proteins Hsp60 and Hsp10 are structurally and functionally nearly identical to GroEL and GroES, respectively, due to their endosymbiotic origin.
HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 belong to a large class of molecules that assist protein folding, called molecular chaperones.
The heat shock response (HSR) is a cell stress response that increases the number of molecular chaperones to combat the negative effects on proteins caused by stressors such as increased temperatures, oxidative stress, and heavy metals. In a normal cell, proteostasis must be maintained because proteins are the main functional units of the cell. Many proteins take on a defined configuration in a process known as protein folding in order to perform their biological functions. If these structures are altered, critical processes could be affected, leading to cell damage or death. The heat shock response can be employed under stress to induce the expression of heat shock proteins (HSP), many of which are molecular chaperones, that help prevent or reverse protein misfolding and provide an environment for proper folding.
A thermosome is a group II chaperonin protein complex that functions in archaea. It is the homolog of eukaryotic CCT. This group II chaperonin is an ATP-dependent chaperonin that is responsible for folding or refolding of incipient or denatured proteins. A thermosome has two rings, each consisting of eight subunits, stacked together to form a cylindrical shape with a large cavity at the center. The thermosome is also defined by its heterooligomeric nature. The complex consists of two subunits that alternate location within its two rings.
Prefoldin (GimC) is a superfamily of proteins used in protein folding complexes. It is classified as a heterohexameric molecular chaperone in both archaea and eukarya, including humans. A prefoldin molecule works as a transfer protein in conjunction with a molecule of chaperonin to form a chaperone complex and correctly fold other nascent proteins. One of prefoldin's main uses in eukarya is the formation of molecules of actin for use in the eukaryotic cytoskeleton.
In humans, the gene T-complex 1, a.k.a. TCP1, encodes the protein TCP-1, a.k.a. T-complex protein 1 subunit alpha.
T-complex protein 1 subunit epsilon is a protein that in humans is encoded by the CCT5 gene.
Prefoldin subunit 1 is a protein that in humans is encoded by the PFDN1 gene.
T-complex protein 1 subunit theta is a protein that in humans is encoded by the CCT8 gene. The CCT8 protein is a component of the TRiC complex.
T-complex protein 1 subunit eta is a protein that in humans is encoded by the CCT7 gene.
T-complex protein 1 subunit delta is a protein that in humans is encoded by the CCT4 gene. The CCT4 protein is a component of the TRiC complex.
T-complex protein 1 subunit zeta is a protein that in humans is encoded by the CCT6A gene.
T-complex protein 1 subunit beta is a protein that in humans is encoded by the CCT2 gene.
T-complex protein 1 subunit gamma is a protein that in humans is encoded by the CCT3 gene.
Prefoldin subunit 4 is a protein that in humans is encoded by the PFDN4 gene.
T-complex protein 1 subunit zeta-2 is a protein that in humans is encoded by the CCT6B gene.
The G beta-gamma complex (Gβγ) is a tightly bound dimeric protein complex, composed of one Gβ and one Gγ subunit, and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanine nucleotide-binding proteins, consist of three subunits, called alpha, beta, and gamma subunits, or Gα, Gβ, and Gγ. When a G protein-coupled receptor (GPCR) is activated, Gα dissociates from Gβγ, allowing both subunits to perform their respective downstream signaling effects. One of the major functions of Gβγ is the inhibition of the Gα subunit.
Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies.
