The heat shock protein (Hsp) Hsp90 is one of the most abundant proteins in the cell. It controls the functional turnover of proteins being involved in protein folding, refolding, transport as well as protein degradation. Co‐chaperones influence Hsp90's activity in different ways, among which the Hsp organizing protein (Hop) was found to inhibit its ATP hydrolysis upon binding. Despite the availability of a number of studies investigating the Hsp90:Hop complex, several aspects of the Hsp90:Hop interaction have remained unresolved. Here, we employed a combinatory approach comprising native polyacrylamide gel electrophoresis, isothermal titration calorimetry, multiangle light scattering, isothermal titration calorimetry, small‐angle X‐ray scattering, dynamic light scattering, and nuclear magnetic resonance, spectroscopy to obtain a comprehensive picture about the human Hsp90β:Hop association in solution. Our data show that only one Hop molecule binds the Hsp90β dimer, Hop can interact with the open and closed state of Hsp90β, and Hop's TPR2A‐2B domains determine the affinity for Hsp90's C‐terminal and middle domain, whereby the interaction with the C‐terminal domain of Hsp90β is sufficient to induce an allosteric conformational change between the two Hsp90β monomers in the Hsp90₂:Hop₁ complex. Together, this study highlights the important role of the co‐chaperone Hop in reorganizing Hsp90 for efficient client loading.

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Hsp90与其伴侣伴侣啤酒花相互作用的分子基础

热休克蛋白（Hsp）Hsp90是细胞中最丰富的蛋白之一。它控制参与蛋白质折叠，重折叠，转运以及蛋白质降解的蛋白质功能转换。伴侣伴侣以不同的方式影响Hsp90的活性，其中发现Hsp组织蛋白（Hop）在结合后会抑制其ATP水解。尽管有许多研究Hsp90：Hop复合物的研究，但Hsp90：Hop相互作用的几个方面仍未解决。在这里，我们采用了一种组合方法，包括天然聚丙烯酰胺凝胶电泳，等温滴定量热，多角度光散射，等温滴定量热，小角度X射线散射，动态光散射和核磁共振，光谱学以获得关于溶液中人Hsp90β：Hop缔合的全面图片。我们的数据表明，只有一个Hop分子结合Hsp90β二聚体，Hop可以与Hsp90β的打开和关闭状态相互作用，而Hop的TPR2A-2B域决定了对Hsp90的C末端和中间域的亲和力，从而与Csp90β的C-末端相互作用。 Hsp90β的末端结构域足以诱导Hsp90中两个Hsp90β单体之间的变构构象变化₂：Hop ₁复合体。总之，这项研究突出了伴侣伴侣啤酒花在重组Hsp90以有效加载客户方面的重要作用。