pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1
pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1
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DOI：
10.1007/s12192-017-0783-z
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发表时间：
2017-07-01
影响因子：
3.8
通讯作者：
Klevit, Rachel E.
中科院分区：
文献类型：
--
作者：
Clouser, Amanda F.;Klevit, Rachel E.
人小分子热休克蛋白（sHSPs）的保持酶活性和寡聚倾向受环境因素的调节。然而，原子级的细节缺乏应激改变sHSP反应的机制。我们以前证明，HSPB 5的调节是由一个单一的保守的组氨酸在生理相关的pH范围6.5-7.5。在这里，我们表明，热休克蛋白B1响应pH值通过类似的机制，通过pH依赖性的结构变化，诱导通过质子化的结构类似的组氨酸。这里提出的结果表明，收购的正电荷，无论是通过质子化的His 124或其取代赖氨酸，降低了α-晶状体蛋白结构域的二聚体界面的稳定性，增加寡聚体的大小，并适度增加分子伴侣的活性。我们的研究结果表明，具有保守的组氨酸的人sHSPs之间的pH值依赖性的结构调节的保守机制，虽然不同的sHSPs的结构调制的功能后果不同。
The holdase activity and oligomeric propensity of human small heat shock proteins (sHSPs) are regulated by environmental factors. However, atomic-level details are lacking for the mechanisms by which stressors alter sHSP responses. We previously demonstrated that regulation of HSPB5 is mediated by a single conserved histidine over a physiologically relevant pH range of 6.5-7.5. Here, we demonstrate that HSPB1 responds to pH via a similar mechanism through pH-dependent structural changes that are induced via protonation of the structurally analogous histidine. Results presented here show that acquisition of a positive charge, either by protonation of His124 or its substitution by lysine, reduces the stability of the dimer interface of the alpha-crystallin domain, increases oligomeric size, and modestly increases chaperone activity. Our results suggest a conserved mechanism of pH-dependent structural regulation among the human sHSPs that possess the conserved histidine, although the functional consequences of the structural modulations vary for different sHSPs.