2026-02-05 マックス・プランク研究所
Artistic view of a living human cell, where sparse fluorescent labels, depicted as light bulbs, illuminate the TRiC chaperonin and ribosome amid molecular complexity. A newly synthesized protein emerging from the ribosome engages with the squid-like prefoldin and is delivered to the barrel-shaped TRiC chaperonin. This method enables real-time single-molecule insight into how proteins are guided along their folding pathway inside the cell.© MPI of Biochemistry/ Marzia Munafo
<関連情報>
- https://www.mpg.de/26083458/dynamic-interaction-between-protein-folding-helpers-and-proteins
- https://www.nature.com/articles/s41586-025-10073-3
生体内TRiCシャペロニンシステムの単分子ダイナミクス Single-molecule dynamics of the TRiC chaperonin system in vivo
Rongqin Li,Niko Dalheimer,Martin B. D. Müller & F. Ulrich Hartl
Nature Published:04 February 2026
DOI:https://doi.org/10.1038/s41586-025-10073-3
Abstract
The essential chaperonin T-complex protein ring complex (TRiC) (also known as chaperonin containing TCP-1 (CCT)) mediates protein folding in cooperation with the co-chaperone prefoldin (PFD)1,2,3,4,5. In vitro experiments have shown that the cylindrical TRiC complex facilitates folding through ATP-regulated client protein encapsulation6,7,8,9. However, the functional dynamics of the chaperonin system in vivo remain unexplored. Here we developed single-particle tracking in human cells to monitor the interactions of TRiC–PFD with newly synthesized proteins. Both chaperones engaged nascent polypeptides repeatedly in brief probing events typically lasting around one second, with PFD recruiting TRiC. As shown with the chaperonin client actin8, the co-translational interactions of PFD and TRiC increased in frequency and lifetime during chain elongation. Close to translation termination, PFD bound for several seconds, facilitating TRiC recruitment for post-translational folding involving multiple reaction cycles of around 2.5 s. Notably, the lifetimes of TRiC interactions with a folding-defective actin mutant were markedly prolonged, indicating that client conformational properties modulate TRiC function. Mutant actin continued cycling on TRiC until it was targeted for degradation. TRiC often remained confined near its client protein between successive binding cycles, suggesting that the chaperonin machinery operates within a localized ‘protective zone’ in which free diffusion is restricted. Together, these findings offer detailed insight into the single-molecule dynamics and supramolecular organization of the chaperonin system in the cellular environment.
