Strand-Swapped SH3 Domain Dimer with Superoxide Dismutase Activity.

IF 10.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Central Science Pub Date : 2025-01-10 eCollection Date: 2025-01-22 DOI:10.1021/acscentsci.4c01347

Florian R Häge, Merlin Schwan, Marcos Rafael Conde González, Jonas Huber, Stefan Germer, Matilde Macrì, Jürgen Kopp, Irmgard Sinning, Franziska Thomas

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Abstract

The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu²⁺-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The resulting low complexity metalloprotein was characterized for structure and function by circular dichroism and UV spectroscopy as well as EPR spectroscopy and X-ray crystallography. The miniprotein was found to be a strand-swapped dimer with an unusual coupled binuclear Type 2-like copper center in each protomer. SO1-Cu was found to be SOD-active with an activity only 1 order of magnitude lower than that of natural SOD enzymes and 1 to 2 orders of magnitude higher than that of other low-complexity SOD protein models of similar size. This serendipitous design provides us with a new structural template for future designs of binuclear metalloproteins with different metal ions and functions.

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具有超氧化物歧化酶活性的交换SH3结构域二聚体。

金属蛋白的设计使我们能够更好地了解蛋白质中的金属络合作用及其产生的功能。在这项研究中，我们将Cu2+结合位点整合到天然蛋白质结构域，58个氨基酸的c-Crk-SH3中，创建了一个小型化的超氧化物歧化酶模型，称为SO1。利用圆二色、紫外光谱、EPR光谱和x射线晶体学对合成的低复杂度金属蛋白进行了结构和功能表征。该微型蛋白是一种链交换二聚体，在每个原聚体中都有一个不寻常的偶联双核2型铜中心。SO1-Cu具有SOD活性，其活性仅比天然SOD酶低1个数量级，比其他类似大小的低复杂性SOD蛋白模型高1 ~ 2个数量级。这种偶然的设计为我们今后设计具有不同金属离子和功能的双核金属蛋白提供了一种新的结构模板。

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来源期刊

ACS Central Science Chemical Engineering-General Chemical Engineering

CiteScore

25.50

自引率

0.50%

发文量

194

审稿时长

10 weeks

期刊介绍： ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.

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