The TRiC/CCT complex is a highly conserved chaperonin comprised of eight paralogous subunits arranged in a ring-like structure; the complex consists of two rings stacked back to back. The CCT complex is known to play a critical role in cytoskeleton protein folding. In Drosophila, there is evidence that components of the TRiC/CCT complex have cardiac-specific functions. Five of the eight Drosophila TRiC/CCT subunits (CCT3, CCT4, CCT5, CCT6, and CCT7) have been investigated in the context of this human disease model; they are orthologous to human genes of the same designation (there 2 CCT6 genes in human, CCT6A and CCT6B).
A UAS construct of the wild-type human Hsap\CCT4 gene has been introduced into flies; functional complementation (heterologous rescue) of phenotypes effected by RNAi targeted to Dmel\CCT4 is observed. None of the other human TRiC/CCT complex genes has been introduced into flies.
Cardiac-specific knock-down of Drosophila TRiC/CCT complex genes, effected by RNAi, results in progressive cardiac defects, including morphological defects and noncontractile regions; cytological defects, including disorganization of cardiac actin- and myosin-containing myofibrils; and shortened lifespan. Disruption of circadian rhythms exacerbates the observed cardiac dysfunction phenotypes. Many physical interactions have been described for the Drosophila CCT genes; see below and in the relevant gene reports.
[updated Apr. 2020 by FlyBase; FBrf0222196]
The role of the cardiac cytoskeleton in cardiomyocyte function is reviewed in Sequeira et al., 2014 (pubmed:23860255).
TRiC/CCT is a highly conserved chaperonin that uses ATP cycling to facilitate folding of approximately 10% of the eukaryotic proteome; the hetero-oligomeric complex consists of two stacked rings of eight paralogous subunits each (Leitner et al., 2012; pubmed:22503819).
The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back. Each ring is composed of eight different but similar subunits and each subunit has three distinct domains. CCT assists folding of actin, tubulin, and numerous other cellular proteins in an ATP-dependent manner. (Kabir et al., 2011; pubmed:22312474)
See the HGNC page titled Gene Family: Chaperonins (https://www.genenames.org/cgi-bin/genefamilies/set/587).
One to one (1 human to 1 Drosophila).
One to one (1 human to 1 Drosophila).
One to one (1 human to 1 Drosophila).
One to one (1 human to 1 Drosophila).
Many to one (2 human to 1 Drosophila).
Many to one (2 human to 1 Drosophila).
High-scoring ortholog of human CCT3 (1 Drosophila to 1 human). Dmel\CCT3 shares 69% identity and 83% similarity with the human gene.
High-scoring ortholog of human CCT4 (1 Drosophila to 1 human). Dmel\CCT4 shares 68% identity and 84% similarity with the human gene.
High-scoring ortholog of human CCT5 (1 Drosophila to 1 human). Dmel\CCT5 shares 71% identity and 88% similarity with the human gene.
High-scoring ortholog of human CCT6A and CCT6B (1 Drosophila to 2 human). Dmel\CCT6 shares 68-69% identity and 84-86% similarity with the human genes.
High-scoring ortholog of human CCT7 (1 Drosophila to 1 human). Dmel\CCT7 shares 75% identity and 86% similarity with the human gene.
