Domain-selective folding of the tandem β-propeller protein Coronin 7 (Coro7) by the chaperonin CCT/TRiC
Year: 2026
Type: article
Abstract: The Chaperonin containing tailless complex polypeptide 1 (CCT) or TCP-1 ring complex (TRiC) plays a central role in maintaining cellular homeostasis by supporting protein folding and damping protein aggregation. Besides the abundant cytoskeletal proteins, actin and tubulin, CCT/TRiC is emerging as an obligate chaperone for WD40 proteins, which are comprised of one or multiple β-propeller domains. To date, only WD40 proteins consisting of a single β-propeller domain have been described as CCT/TRiC substrates. Using a combination of biotin proximity ligation, mass spec analysis and co-immunoprecipitation, we here identify the tandem β-propeller protein, Coronin 7 (Coro7), as a novel CCT/TRiC interactor. Transient knockdown of CCT/TRiC further severely diminished expression of Coro7, suggesting that Coro7 is a bona fide CCT/TRiC substrate. Interestingly, co-immunoprecipitation of truncated Coro7 proteins demonstrated that CCT/TRiC only interacts with the first β-propeller domain of Coro7. In line with this, fusion of a miniTurboID tag to the N- or C-terminus of Coro7 showed significant enrichment of all CCT/TRiC subunits for the first, but not the second β-propeller domain. Similarly, co-immunoprecipitation with individual Coro7 β-propeller domains generated by introduction of a protease cleavage site in full length Coro7, confirmed that CCT/TRiC only binds to the first β-propeller domain. Altogether, our study shows that CCT/TRiC can also function as a chaperone for multi-β-propeller domain proteins, likely by initiating the folding of the first β-propeller domain, which can then help template autonomous folding of consecutive β-propeller domains.
Source: Journal of Biological Chemistry
Institution: Washington University in St. Louis
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,430
Funders: Institute of Clinical and Translational Sciences, Alvin J. Siteman Cancer Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Washington University School of Medicine in St. Louis, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
OpenAlex ID: W7127896688