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Domain-selective folding of the tandem β-propeller protein Coronin 7 by the chaperonin CCT/TRiC

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 the β-propeller domain of WD40 proteins. 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, co-immunoprecipitation, and knockdown studies, we here identify the tandem β-propeller protein, Coronin 7 (Coro7), as a novel substrate of CCT/TRiC. This raised the question how CCT/TRiC can fold a protein that is too large to fit into its folding chamber, but consists of two domains that require its folding. Surprisingly, co-immunoprecipitation of truncated Coro7 proteins or cleaved full length Coro7 demonstrated that CCT/TRiC only interacts with the first β-propeller domain (PropA) of Coro7. Further experiments showed that CCT/TRiC preferentially binds to PropA, independently of whether this domain is situated at the N- or C-terminus of Coro7. This strongly suggests that CCT/TRiC does not identify β-propeller substrates by their topology, but instead developed specific ways to recognize β-propeller sequences that require folding.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293t Cell

SUBMITTER: DeHaven McCrary

LAB HEAD: Silvia Jansen

PROVIDER: PXD073687 | Pride | 2026-02-20

REPOSITORIES: Pride

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			Action	DRS
	Figure1_Blank_1.raw	Raw
	Figure1_Blank_2.raw	Raw
	Figure1_Blank_3.raw	Raw
	Figure1_Coro7_1.mgf	Mgf
	Figure1_Coro7_1.raw	Raw

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