Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.
Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.
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心血管小热休克蛋白 HSPB7 是一种动力学特权反应亲电物质 (RES) 传感器。
DOI：
10.1021/acschembio.7b00925
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发表时间：
2018
影响因子：
4
通讯作者：
Aye,Yimon
中科院分区：
文献类型：
--
作者：
Surya,SanjnaL;Long,MarcusJC;Urul,DanielA;Zhao,Yi;Mercer,EmilyJ;EIsaid,IslamM;Evans,Todd;Aye,Yimon
小分子热休克蛋白（Small heat shock protein，sHSP）-B7（HSPB 7）是一种非ATP依赖的肌肉特异性sHSP。HSPB 7的确切作用是谜。在这里，我们公开了斑马鱼Hspb 7是一种动力学特权传感器，能够与天然反应性亲电物质（RES）迅速反应，当只有亚化学计量的RES接近活细胞中表达的Hspb 7时。在两个Hspb 7-半胱氨酸中，这种RES传感由单个半胱氨酸（C117）实现。体外纯化和表征表明，RES加合速率是蛋白质-半胱氨酸与天然羰基基RES的最有效的报道之一。共价配体结合伴随着结构变化（β-片层含量增加），基于圆二色性分析。在这两个半胱氨酸，只有C117是保守的脊椎动物，我们表明，人类的直系同源物也能够在细胞中的RES传感。此外，癌症相关的错义突变降低了这种RES传感特性。这种进化上保守的半胱氨酸生物传感器可能在心脏保护中发挥氧化还原调节作用。
Small heat shock protein (sHSP)-B7 (HSPB7) is a muscle-specific member of the non-ATP-dependent sHSPs. The precise role of HSPB7 is enigmatic. Here, we disclose that zebrafish Hspb7 is a kinetically privileged sensor that is able to react rapidly with native reactive electrophilic species (RES), when only substoichiometric amounts of RES are available in proximity to Hspb7 expressed in living cells. Among the two Hspb7-cysteines, this RES sensing is fulfilled by a single cysteine (C117). Purification and characterizationsin vitroreveal that the rate for RES adduction is among the most efficient reported for protein-cysteines with native carbonyl-based RES. Covalent-ligand binding is accompanied by structural changes (increase in β-sheet-content), based on circular dichroism analysis. Among the two cysteines, only C117 is conserved across vertebrates; we show that the human ortholog is also capable of RES sensing in cells. Furthermore, a cancer-relevant missense mutation reduces this RES-sensing property. This evolutionarily conserved cysteine-biosensor may play a redox-regulatory role in cardioprotection.