2026年2月4日，马克斯·普朗克生物化学研究所F. Ulrich Hartl团队在《自然》杂志发表论文，宣布他们的最新研究提出了体内TRiC伴侣蛋白系统的单分子动力学。

在这里，该课题组研究人员在人类细胞中开发了单粒子跟踪，以监测TRiC–PFD与新合成蛋白的相互作用。两种伴侣蛋白都在短暂的探测过程中重复使用新生多肽，通常持续约一秒钟，PFD招募TRiC。正如伴侣蛋白客户端肌动蛋白所示，在链延伸期间，PFD和TRiC的共翻译相互作用的频率和寿命增加。在接近翻译终止时，PFD结合了几秒钟，促进了TRiC的招募，用于翻译后折叠，涉及约2.5 s的多个反应周期。

值得注意的是，TRiC与有折叠缺陷的肌动蛋白突变体相互作用的寿命明显延长，表明客户端构象特性调节了TRiC的功能。突变的肌动蛋白继续在TRiC上循环，直到它成为降解的目标。在连续的结合周期之间，它经常被限制在其客户蛋白附近，这表明伴侣蛋白机制在一个局部的“保护区域”内运作，在这个区域内自由扩散受到限制。总之，这些发现为细胞环境中伴侣蛋白系统的单分子动力学和超分子组织提供了详细的见解。

研究人员表示，必需伴侣蛋白t复合物蛋白环复合物（TRiC）（也称为含有TCP-1的伴侣蛋白（CCT））与共伴侣蛋白前折叠蛋白（PFD）协同介导蛋白质折叠。体外实验表明，圆柱形TRiC复合体通过ATP调控的客户蛋白包封促进折叠。然而，伴侣蛋白系统在体内的功能动力学仍未被探索。

附：英文原文

Title: Single-molecule dynamics of the TRiC chaperonin system in vivo

Author: Li, Rongqin, Dalheimer, Niko, Mller, Martin B. D., Hartl, F. Ulrich

Issue&Volume: 2026-02-04

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 2.5s. 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.

DOI: 10.1038/s41586-025-10073-3

Source: https://www.nature.com/articles/s41586-025-10073-3