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 characterizations in vitro reveal 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.

中文翻译：

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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

小热休克蛋白 (sHSP)-B7 (HSPB7) 是非 ATP 依赖性 sHSP 的肌肉特异性成员。HSPB7 的确切作用是个谜。在这里，我们公开了斑马鱼 Hspb7 是一种动力学上优先的传感器，当活细胞中表达的 Hspb7 附近只有亚化学计量的 RES 时，它能够与天然反应性亲电子物质 (RES) 快速反应。在两个 Hspb7-半胱氨酸中，这种 RES 感应是由单个半胱氨酸 (C117) 实现的。体外纯化和表征表明，RES 加合速率是已报道的具有天然羰基 RES 的蛋白质半胱氨酸中最有效的速率之一。根据圆二色性分析，共价配体结合伴随着结构变化（β-折叠含量增加）。在这两个半胱氨酸中，只有 C117 在脊椎动物中是保守的；我们证明人类直系同源物也能够在细胞中进行 RES 传感。此外，与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。