Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
Department of Chemical Biology, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383, Wrocław, Poland.
Cell Commun Signal. 2022 Oct 24;20(1):163. doi: 10.1186/s12964-022-00980-7.
Nesfatin-1 and -2 are produced from a reaction in which the N-terminus of human Nucleobindin-2 undergoes proteolytical processing. To date, Nucleobindin-2 and/or nesfatin-1 have only been shown to act as peptide hormones. On the other hand, the purpose of nesfatin-2 remains unknown. Since Nucleobindin-2/nesfatin-1 is thought impact the control of a wide range of physiological processes, including energy homeostasis, neurodegenerative processes and carcinogenesis, its ligands/interactions deserve special studies and attention. However, there are no reports about the molecular properties of the proteolytical products of human Nucleobindin-2 in the literature. Hence, this study aimed to analyze the effect of Zn(II) and Ca(II) on human nesfatin-1, -2, and -1/2 structures. Herein, we report that human nesfatin-1 is a member of the intrinsically disordered protein family, as indicated by circular dichroism and analytical ultracentrifugation experiments. In contrast, we found that the human nesfatin-2 and nesfatin-1/2 structures were globular with intrinsically disordered regions. Under Zn(II) treatment, we observed concentration-dependent structurization and compaction of intrinsically disordered nesfatin-1 and its propensity for oligomerization, as well as destabilization of both nesfatin-2 and nesfatin-1/2. Furthermore, dissociation constants for Zn(II) binding by nesfatin-1, nesfatin-2, and nesfatin-1/2 were also reported. Moreover, structurally distinct nesfatin-1 and -2 seem to be interdependent when linked together, as indicated by the observed molecular properties of nesfatin-1/2, which in turn are not a simple sum of the properties exhibited by the former peptides. Thus, herein, we shed new light on the molecular behavior of human nesfatins, which might help to elucidate the complex function of those peptides. Video abstract.
nesfatin-1 和 -2 是由人类 Nucleobindin-2 的 N 端发生蛋白水解加工反应产生的。迄今为止，Nucleobindin-2 和/或 nesfatin-1 仅被证明作为肽激素发挥作用。另一方面，nesfatin-2 的目的尚不清楚。由于 Nucleobindin-2/nesfatin-1 被认为影响包括能量平衡、神经退行性过程和癌变在内的广泛生理过程的控制，其配体/相互作用值得特别研究和关注。然而，文献中没有关于人类 Nucleobindin-2 蛋白水解产物的分子特性的报道。因此，本研究旨在分析 Zn(II) 和 Ca(II) 对人 nesfatin-1、-2 和 -1/2 结构的影响。在此，我们报告人 nesfatin-1 是一种无序蛋白家族的成员，这是由圆二色性和分析超速离心实验表明的。相比之下，我们发现人 nesfatin-2 和 nesfatin-1/2 结构是球状的，具有无规卷曲区域。在 Zn(II) 处理下，我们观察到无规卷曲的 nesfatin-1 及其寡聚化倾向的浓度依赖性结构化和紧凑化，以及 nesfatin-2 和 nesfatin-1/2 的不稳定性。此外，还报告了 nesfatin-1、nesfatin-2 和 nesfatin-1/2 与 Zn(II) 结合的解离常数。此外，连接在一起的结构不同的 nesfatin-1 和 -2 似乎是相互依赖的，这表明 nesfatin-1/2 的观察到的分子特性，而反过来，这些特性不是前两种肽表现出的特性的简单总和。因此，在此，我们揭示了人类 nesfatin 的分子行为的新亮点，这可能有助于阐明这些肽的复杂功能。视频摘要。
