# Domain-selective folding of the tandem β-propeller protein Coronin 7 (Coro7) by the chaperonin CCT/TRiC

## TL;DR

This study shows that the chaperonin CCT/TRiC folds only the first β-propeller domain of the large Coronin 7 protein, revealing a new mechanism for domain-selective folding.

## Contribution

The paper identifies Coronin 7 as a novel CCT/TRiC substrate and reveals domain-selective folding of tandem β-propeller proteins.

## Key findings

- CCT/TRiC interacts only with the first β-propeller domain of Coronin 7.
- CCT/TRiC preferentially binds to the first β-propeller domain regardless of its position in the protein.
- CCT/TRiC recognizes β-propeller domains based on sequence rather than topology.

## 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 of Coro7. Further experiments showed that CCT/TRiC preferentially binds to the first β-propeller, 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.