Hsp90 Oligomers Interacting with the Aha1 Cochaperone: An Outlook for the Hsp90 Chaperone Machineries
Hsp90 Oligomers Interacting with the Aha1 Cochaperone: An Outlook for the Hsp90 Chaperone Machineries
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DOI：
10.1021/acs.analchem.5b00051
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发表时间：
2015-07-21
影响因子：
7.4
通讯作者：
Garnier, Cyrille
中科院分区：
文献类型：
--
作者：
Lepvrier, Eleonore;Mollintraffort, Laura;Garnier, Cyrille
热休克蛋白90（Hsp 90）是一种高度柔性的二聚体，在二价阳离子存在下或在热休克下能够自缔合。本研究探讨了热休克蛋白90寡聚体和热休克蛋白90辅助伴侣蛋白Ahal（热休克蛋白90 ATP酶激活剂）之间的关系。Ahal与热休克蛋白90二聚体和寡聚体的相互作用进行了评价，通过超离心，尺寸排阻色谱耦合多角度激光光散射和高质量基质辅助激光解吸/电离飞行时间质谱。Hsp 90二聚体能够结合多达四个Ahal分子，并且Hsp 90寡聚体也能够与Ahal相互作用。Ahal的结合不干扰Hsp 90寡聚化过程。除了Hsp 90二聚体，相互作用的化学计量保持恒定，在2 Ahal分子/Hsp 90二聚体，无论Hsp 90寡聚化的程度。此外，Ahal主要结合Hsp 90寡聚体。因此，Hsp 90寡聚体结合Ahal ATP酶激活剂的能力增强了它们在Hsp 90分子伴侣机制中的作用。
The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer able to self-associate in the presence of divalent cations or under heat shock. This study investigated the relationship between Hsp90 oligomers and the Hsp90 cochaperone Ahal (activator of Hsp90 ATPase). The interactions of Ahal with Hsp90 dimers and oligomers were evaluated by ultracentrifugation, size-exclusion chromatography coupled to multiangle laser light scattering and high-mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Hsp90 dimer was able to bind up to four Ahal molecules, and Hsp90 oligomers are also able to interact with Ahal. The binding of Ahal did not interfere with the Hsp90 oligomerization process. Except for Hsp90 dimer, the stoichiometry of the interaction remained constant, at 2 Ahal molecules per Hsp90 dimer, regardless of the degree of Hsp90 oligomerization. Moreover, Ahal predominantly bound to Hsp90 oligomers. Thus, the ability of Hsp90 oligomers to bind the Ahal ATPase activator reinforces their role within the Hsp90 chaperone machineries.