School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, China.
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, China; School of Chemical Engineering and Food Science, Zhengzhou Institute of Technology, Zhengzhou 450044, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jan 5;224:117401. doi: 10.1016/j.saa.2019.117401. Epub 2019 Jul 19.
Polypeptides with finger-like structures can often intercalate into the grooves of DNA, thereby affecting DNA repair or activating gene transcription, both of which are crucial for the regulation of physiological processes. Their conserved amino acid sequence and simple structure have provided useful elements for the design and assembly of functional molecules. In this paper, using the CH zinc finger domain and the PEP-FOLD3 online simulation platform 11 polypeptides containing 22 amino acid residues were designed. In addition, the CD spectroscopy was combined with the fluorescence spectroscopy to study the polypeptide structures and their interaction with DNA. Results showed that although addition of zinc ions affected the polypeptide structure, particularly of the polypeptides A4, B1, and B3, zinc ion was not an essential factor for increasing polypeptide-DNA interactions. Our study revealed an increase in the interaction strength between mutated polypeptides and DNA, suggesting that mutations disrupt polypeptide structure, and polypeptides interact with DNA by groove and electrostatic binding. Mutations at the 12th and 15th amino acid residues had the greatest effect. The stronger binding between A2 or B2 and DNA indicates that the polypeptide has a spatial structure that can stably interact with DNA. The structure and characteristics of these polypeptide domains can provide information for the design and development of new polypeptide functional molecules, which could have potential significance and applications. However, this information also suggests that there are many challenges facing polypeptide design due to the synergistic effects between the side chains of amino acid residues.
具有指状结构的多肽通常可以插入到 DNA 的沟槽中，从而影响 DNA 修复或激活基因转录，这两者对于生理过程的调控都至关重要。其保守的氨基酸序列和简单的结构为功能分子的设计和组装提供了有用的元素。在本文中，我们使用 CH 锌指结构域和 PEP-FOLD3 在线模拟平台设计了 22 个氨基酸残基组成的 11 个多肽。此外，我们还结合圆二色光谱和荧光光谱研究了多肽结构及其与 DNA 的相互作用。结果表明，尽管锌离子的加入会影响多肽结构，尤其是 A4、B1 和 B3 这三种多肽，但锌离子并不是增加多肽-DNA 相互作用的必要因素。我们的研究揭示了突变多肽与 DNA 之间相互作用强度的增加，这表明突变会破坏多肽结构，而多肽通过沟槽和静电结合与 DNA 相互作用。第 12 和第 15 个氨基酸残基的突变影响最大。A2 或 B2 与 DNA 的结合更强，表明多肽具有可以与 DNA 稳定相互作用的空间结构。这些多肽结构域的结构和特征为设计和开发新的多肽功能分子提供了信息，这可能具有重要意义和应用价值。然而，由于氨基酸残基侧链之间的协同作用，多肽设计也面临着许多挑战。
