Background

Amyloids are highly ordered polypeptide aggregates stabilized by a beta-sheet structural core. Though classically associated to pathology, reports on novel functional roles of these proteins have increasingly emerged in the past decade. Moreover, the recent discovery that amyloids formed with rationally designed small peptides can exhibit catalytic reactivity has opened up new opportunities in both biology and biotechnology. The observed activities typically require the binding of divalent metals, giving rise to active metal-amyloid complexes.

Methods

Peptide (SDIDVFI) was aggregated in vitro. The structure of the self-assembled species was analyzed using fluorescence, transmission electron microscopy, circular dichroism and computational modeling. A kinetic characterization of the emerging catalytic activity was performed.

Results

The peptide self-assembled into canonical amyloids that exhibited catalytic activity towards hydrolysis of the phosphoanhydride bonds of adenosine triphosphate (ATP), partially mimicking an ATPase-like enzyme. Both amyloid formation and activity are shown to depend on manganese (Mn²⁺) binding. The activity was not restricted to ATP but also affected all other ribonucleotides (GTP, CTP and UTP). Peptides carrying a single aspartate exhibited a similar activity.

Conclusions

The phosphoanhydride bonds appear as the main specificity target of the Mn²⁺-amyloid complex. A single aspartate per peptide is sufficient to enable the hydrolytic activity.

General significance

Catalytic amyloids are shown for the first time to catalyze the hydrolysis of all four ribonucleotides. Our results should contribute towards understanding the biological implications of amyloid-mediated reactivity as well as in the design of future catalytic amyloids for biotechnological applications.

中文翻译：

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催化淀粉样蛋白显示的ATPase样活性的功能表征。

背景

淀粉样蛋白是通过β-折叠结构核心稳定的高度有序的多肽聚集体。尽管通常与病理学相关，但是在过去的十年中，有关这些蛋白质的新功能作用的报道越来越多。而且，最近发现由合理设计的小肽形成的淀粉样蛋白可以表现出催化反应性的发现为生物学和生物技术开辟了新的机遇。观察到的活性通常需要二价金属的结合，从而产生活性金属-淀粉样复合物。

方法

肽（SDIDVFI）在体外聚集。利用荧光，透射电子显微镜，圆二色性和计算模型分析了自组装物种的结构。进行了新兴催化活性的动力学表征。

结果

该肽自组装成典型的淀粉样蛋白，该淀粉样蛋白对三磷酸腺苷（ATP）的磷酸酐键的水解具有催化活性，部分模拟了ATPase-like酶。淀粉样蛋白的形成和活性均取决于锰（Mn ²⁺）的结合。该活性不仅限于ATP，还影响所有其他核糖核苷酸（GTP，CTP和UTP）。带有单个天冬氨酸的肽表现出相似的活性。

结论

磷酸酐键似乎是Mn 2 ^+-淀粉样复合物的主要特异性靶标。每个肽单一的天冬氨酸足以实现水解活性。

一般意义

首次显示出催化淀粉样蛋白催化所有四个核糖核苷酸的水解。我们的研究结果应有助于理解淀粉样蛋白介导的反应性的生物学意义，以及未来生物技术应用中催化淀粉样蛋白的设计。