Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network

Intracellular protein homeostasis is maintained by a network of chaperones that function to fold proteins into their native conformation. The eukaryotic TRiC chaperonin (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1) facilitates folding of a subset of proteins with folding constraints such as complex topologies. To better understand the mechanism of TRiC folding, we investigated the biogenesis of an obligate TRiC substrate, the reovirus sigma 3 capsid protein. We discovered that the sigma 3 protein interacts with a network of chaperones, including TRiC and prefoldin. Using a combination of cryoelectron microscopy, cross-linking mass spectrometry, and biochemical approaches, we establish functions for TRiC and prefoldin in folding sigma 3 and promoting its assembly into higher-order oligomers. These studies illuminate themolecular dynamics of sigma 3 folding and establish a biological function for TRiC in virus assembly. In addition, our findings provide structural and functional insight into the mechanism by which TRiC and prefoldin participate in the assembly of protein complexes.

Automated summary

The TRiC chaperonin plays a crucial role in folding and assembly of the reovirus sigma 3 capsid protein, interacting with a network of chaperones including prefoldin. This study sheds light on the molecular dynamics of sigma 3 folding and establishes a biological function for TRiC in virus assembly, while also providing structural and functional insights into how TRiC and prefoldin participate in protein complex assembly.