Nuclear TRiC states captured in situ

The chaperonin T-complex protein ring complex (TRiC) is an essential protein-folding machine in eukaryotic cells. Although its cytosolic role in folding newly synthesized proteins is well established, nuclear TRiC remains less well described. Here, we combined cryo-electron tomography (cryo-ET), cross-linking and affinity purification mass spectrometry with AlphaFold3 (AF3)-based structural modeling to examine nuclear TRiC in human cells. We detected intermediates of the TRiC duty cycle in the nucleus and identified several nuclear proteins that bind to TRiC. The respective AF3 models suggest interaction surfaces at the inside of the TRiC chamber. Our findings point toward compartment-specific roles of TRiC and a potential function in maintaining nuclear proteostasis. By data-mining very large datasets, our study establishes that rather low-abundant events can be analyzed by cryo-ET. It thus paves the way toward broader applications.