Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA.
Chemistry. 2018 Oct 17;24(58):15685-15690. doi: 10.1002/chem.201803933. Epub 2018 Sep 19.
Fundamental research on Parkinson's disease (PD) most often focuses on the ability of α-synuclein (aS) to form oligomers and amyloids, and how such species promote brain cell death. However, there are indications that aS also plays a gene-regulatory role in the cell nucleus. Here, the interaction between monomeric aS and DNA in vitro has been investigated with single-molecule techniques. Using a nanofluidic channel system, it was discovered that aS binds to DNA and by studying the DNA-protein complexes at different confinements we determined that aS binding increases the persistence length of DNA from 70 to 90 nm at high coverage. By atomic force microscopy it was revealed that at low protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein. As DNA-aS interactions may play roles in PD, it is of importance to characterize biophysical properties of such complexes in detail.
帕金森病（PD）的基础研究通常集中在α-突触核蛋白（aS）形成寡聚物和淀粉样纤维的能力上，以及这些物质如何促进脑细胞死亡。然而，有迹象表明，aS 也在细胞核中发挥基因调控作用。在这里，使用单分子技术研究了单体 aS 与 DNA 之间的体外相互作用。通过纳米流控通道系统，发现 aS 与 DNA 结合，并通过在不同限制条件下研究 DNA-蛋白质复合物，我们确定 aS 结合将 DNA 的持久长度从高覆盖率下的 70 纳米增加到 90 纳米。原子力显微镜揭示，在低蛋白与 DNA 的比例下，aS 结合发生在沿着 DNA 分散的小蛋白簇中；在高蛋白与 DNA 的比例下，DNA 完全被蛋白质覆盖。由于 DNA-aS 相互作用可能在 PD 中发挥作用，因此详细描述这种复合物的生物物理特性非常重要。
