The Hsp40/Hsp70 chaperone families combine versatile folding capacity with high substrate specificity, which is mainly facilitated by Hsp40s. The structure and function of many Hsp40s remain poorly understood, particularly oligomeric Hsp40s that suppress protein aggregation. Here, we used a combination of biochemical and structural approaches to shed new light on the domain interactions of the Hsp40 DnaJB8, and how they regulate recruitment of partner Hsp70s. We identify an interaction between the J-Domain (JD) and C-terminal domain (CTD) of DnaJB8 that sequesters the JD surface, preventing Hsp70 interaction. We propose a new model for DnaJB8-Hsp70 regulation, whereby the JD-CTD interaction of DnaJB8 acts as a reversible autoinhibitory switch that can control the binding of Hsp70. These findings suggest that the evolutionarily conserved CTD of DnaJB8 is a regulatory element of chaperone activity in the proteostasis network.

中文翻译：

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自动调节J域相互作用控制Hsp70募集到DnaJB8伴侣

Hsp40 / Hsp70伴侣家族结合了多种折叠能力和高底物特异性，这主要是由Hsp40促进的。许多Hsp40的结构和功能仍然知之甚少，特别是抑制蛋白质聚集的寡聚Hsp40。在这里，我们结合了生物化学和结构方法，为Hsp40 DnaJB8的结构域相互作用以及它们如何调节Hsp70的募集提供了新的思路。我们发现隔离DnaJB8的J-域（JD）和C末端域（CTD）之间的相互作用，隔离JD表面，防止Hsp70相互作用。我们提出了DnaJB8-Hsp70调节的新模型，其中DnaJB8的JD-CTD相互作用充当可逆的自抑制开关，可以控制Hsp70的结合。