多伴侣蛋白凝聚体增强了内质网中的蛋白质折叠，这一成果由瑞士巴塞尔大学Sebastian Hiller研究组经过不懈努力而取得。2025年8月11日出版的《自然—细胞生物学》发表了这项成果。

在这里，该课题组报告了在蛋白质折叠稳态过程中，在内质网腔中发现的多伴侣蛋白凝聚物，它是在伴侣蛋白PDIA6周围形成的。冷凝物以Ca²⁺依赖的方式形成，研究人员在原子和细胞水平上解决了潜在的机制。PDIA6凝聚体募集更多的伴侣蛋白——Hsp70 BiP、j结构域蛋白ERdj3、二硫异构酶PDIA1和Hsp90 grp94——它们构成了早期折叠机制的一些重要组成部分。伴侣凝聚物增强蛋白质的折叠，如胰岛素原，并防止蛋白质在内质网管内错误折叠。因此，PDIA6支架的伴侣蛋白凝聚物为动态ER伴侣蛋白网络的时空协调提供了功能基础。

据了解，内质网（ER）中的蛋白质折叠依赖于一个分子伴侣网络，该网络促进了客户蛋白的折叠和成熟。然而，内质网伴侣如何以超分子方式组织以发挥其协同作用仍不清楚。

附：英文原文

Title: A multichaperone condensate enhances protein folding in the endoplasmic reticulum

Author: Leder, Anna, Mas, Guillaume, Szentgyrgyi, Viktria, Jakob, Roman P., Maier, Timm, Spang, Anne, Hiller, Sebastian

Issue&Volume: 2025-08-11

Abstract: Protein folding in the endoplasmic reticulum (ER) relies on a network of molecular chaperones that facilitates the folding and maturation of client proteins. How the ER chaperones organize in a supramolecular manner to exert their cooperativity has, however, remained unclear. Here we report the discovery of a multichaperone condensate in the ER lumen, which is formed around the chaperone PDIA6 during protein folding homeostasis. The condensates form in a Ca2+-dependent manner and we resolve the underlying mechanism at the atomic and cellular levels. The PDIA6 condensates recruit further chaperones—Hsp70 BiP, J-domain protein ERdj3, disulfide isomerase PDIA1 and Hsp90 Grp94—which constitute some of the essential components of the early folding machinery. The chaperone condensates enhance folding of proteins, such as proinsulin, and prevent protein misfolding in the ER lumen. The PDIA6-scaffolded chaperone condensates hence provide the functional basis for spatial and temporal coordination of the dynamic ER chaperone network.

DOI: 10.1038/s41556-025-01730-w

Source: https://www.nature.com/articles/s41556-025-01730-w