Rimon Oded, Suss Ohad, Goldenberg Mor, Fassler Rosi, Yogev Ohad, Amartely Hadar, Propper Guy, Friedler Assaf, Reichmann Dana
1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
2 Institute of Chemistry, The Hebrew University of Jerusalem , Safra Campus Givat Ram, Jerusalem, Israel .
Antioxid Redox Signal. 2017 Nov 20;27(15):1252-1267. doi: 10.1089/ars.2016.6900. Epub 2017 Apr 10.
A recently discovered group of conditionally disordered chaperones share a very unique feature; they need to lose structure to become active as chaperones. This activation mechanism makes these chaperones particularly suited to respond to protein-unfolding stress conditions, such as oxidative unfolding. However, the role of this disorder in stress-related activation, chaperone function, and the crosstalk with other chaperone systems is not yet clear. Here, we focus on one of the members of the conditionally disordered chaperones, a thiol-redox switch of the bacterial proteostasis system, Hsp33.
By modifying the Hsp33's sequence, we reveal that the metastable region has evolved to abolish redox-dependent chaperone activity, rather than enhance binding affinity for client proteins. The intrinsically disordered region of Hsp33 serves as an anchor for the reduced, inactive state of Hsp33, and it dramatically affects the crosstalk with the synergetic chaperone system, DnaK/J. Using mass spectrometry, we describe the role that the metastable region plays in determining client specificity during normal and oxidative stress conditions in the cell. Innovation and Conclusion: We uncover a new role of protein plasticity in Hsp33's inactivation, client specificity, crosstalk with the synergistic chaperone system DnaK/J, and oxidative stress-specific interactions in bacteria. Our results also suggest that Hsp33 might serve as a member of the house-keeping proteostasis machinery, tasked with maintaining a "healthy" proteome during normal conditions, and that this function does not depend on the metastable linker region. Antioxid. Redox Signal. 27, 1252-1267.
最近发现的一组条件性无序伴侣蛋白具有一个非常独特的特征；它们需要失去结构才能激活成为伴侣蛋白。这种激活机制使这些伴侣蛋白特别适合应对蛋白质解折叠应激条件，如氧化解折叠。然而，这种无序在应激相关激活、伴侣蛋白功能以及与其他伴侣蛋白系统的相互作用中的作用尚不清楚。在这里，我们聚焦于条件性无序伴侣蛋白的一个成员，细菌蛋白质稳态系统的硫醇 - 氧化还原开关Hsp33。
通过修饰Hsp33的序列，我们发现亚稳区的进化是为了消除氧化还原依赖性伴侣蛋白活性，而不是增强对底物蛋白的结合亲和力。Hsp33的内在无序区域作为其还原的非活性状态的锚定物，并且极大地影响与协同伴侣蛋白系统DnaK/J的相互作用。使用质谱分析，我们描述了亚稳区在细胞正常和氧化应激条件下决定底物特异性中所起的作用。创新与结论：我们揭示了蛋白质可塑性在Hsp33的失活、底物特异性、与协同伴侣蛋白系统DnaK/J的相互作用以及细菌中氧化应激特异性相互作用中的新作用。我们的结果还表明，Hsp33可能作为管家蛋白质稳态机制的一员，负责在正常条件下维持“健康”的蛋白质组，并且该功能不依赖于亚稳连接区。《抗氧化与氧化还原信号》27卷，1252 - 1267页 。
