Calpain is a Ca²⁺‐activated, heterodimeric cysteine protease consisting of a large catalytic subunit and a small regulatory subunit. Dysregulation of this enzyme is involved in a range of pathological conditions such as cancer, Alzheimer's disease and rheumatoid arthritis, and thus calpain I is a drug target with potential therapeutic applications. Difficulty in the production of this enzyme has hindered structural and functional investigations in the past, although heterodimeric calpain I can be generated by Escherichia coli expression in low yield. Here, an unexpected structure discovered during crystallization trials of heterodimeric calpain I (CAPN1C115S + CAPNS1ΔGR) is reported. A novel co‐crystal structure of the PEF(S) domain from the dissociated regulatory small subunit of calpain I and the RNA‐binding chaperone Hfq, which was likely to be overproduced as a stress response to the recombinant expression conditions, was obtained, providing unexpected insight in the chaperone function of Hfq.

中文翻译：

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钙蛋白酶 PEF(S) 结构域与 Hfq 的意外共晶结构揭示了 Hfq 的潜在伴侣功能。

钙蛋白酶是一种 Ca ²⁺激活的异二聚半胱氨酸蛋白酶，由一个大的催化亚基和一个小的调节亚基组成。这种酶的失调与癌症、阿尔茨海默病和类风湿性关节炎等一系列病理状况有关，因此钙蛋白酶 I 是具有潜在治疗应用的药物靶点。尽管异二聚钙蛋白酶 I 可以通过大肠杆菌表达以低产率产生，但这种酶的生产困难阻碍了过去的结构和功能研究。在此，报告了异二聚钙蛋白酶 I (CAPN1C115S + CAPNS1ΔGR) 结晶试验期间发现的意想不到的结构。获得了钙蛋白酶 I 解离调节小亚基和 RNA 结合分子伴侣 Hfq 的 PEF(S) 结构域的新型共晶结构，该结构可能由于对重组表达条件的应激反应而过量产生，从而提供了对 Hfq 的伴侣功能的意外见解。