For many chaperones, a propensity to self-assemble correlates with function. The highly efficient amyloid suppressing chaperone DNAJB6b has been reported to oligomerize. A key question is whether the DNAJB6b self-assemblies or their subunits are active units in the suppression of amyloid formation. Here, we address this question using a nonmodified chaperone. We use the well-established aggregation kinetics of the amyloid β 42 peptide (Aβ42) as a readout of the amyloid suppression efficiency. The experimental setup relies on the slow dissociation of DNAJB6b assemblies upon dilution. We find that the dissociation of the chaperone assemblies correlates with its ability to suppress fibril formation. Thus, the data show that the subunits of DNAJB6b assemblies rather than the large oligomers are the active forms in amyloid suppression. Our results provide insights into how DNAJB6b operates as a chaperone and illustrate the importance of established assembly equilibria and dissociation rates for the design of kinetic experiments.

中文翻译：

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DNAJB6b 抑制淀粉样蛋白形成的能力取决于伴侣聚集状态

对于许多伴侣来说，自组装的倾向与功能相关。据报道，高效淀粉样蛋白抑制分子伴侣 DNAJB6b 会发生寡聚化。一个关键问题是 DNAJB6b 自组装或其亚基是否是抑制淀粉样蛋白形成的活性单位。在这里，我们使用未经修饰的伴侣来解决这个问题。我们使用淀粉样蛋白 β 42 肽 (Aβ42) 的成熟聚集动力学作为淀粉样蛋白抑制效率的读数。实验装置依赖于稀释后 DNAJB6b 组装体的缓慢解离。我们发现伴侣组件的解离与其抑制原纤维形成的能力相关。因此，数据表明 DNAJB6b 组装体的亚基而不是大寡聚体是淀粉样蛋白抑制的活性形式。我们的结果提供了对 DNAJB6b 如何作为伴侣发挥作用的见解，并说明了建立的组装平衡和解离速率对于动力学实验设计的重要性。