Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CSIR unit), Mysore-570020, India.
Front Biosci (Landmark Ed). 2010 Jan 1;15(2):418-36. doi: 10.2741/3628.
Emerging evidences on the nuclear localization of alpha-Synuclein in neurons and a close look in to its primary sequence/structural organization led us to examine its DNA binding ability. Subsequently, we first time demonstrated the interaction of DNA with alpha-Synuclein which was also confirmed by others. We recently showed that double-stranded oligos induce partial folding in alpha-Synuclein and promote its aggregation, where as single-strand circular DNA and supercoiled plasmid DNA induced a helix-rich conformation and protected the protein from fibrillation. In turn, alpha-Synuclein modulates DNA conformation from B- to an altered B-form, which may affect DNA transactions. Interestingly, amyloid-beta peptides and prion proteins implicated in Alzheimer's disease and Prion diseases respectively, were also shown to have DNA binding activity which suggests that DNA binding may be a common property of many amyloidogenic proteins associated with various neurodegenerative disorders. In this review, we debate the biological significance of DNA-alpha-Synuclein interactions; it's beneficial vs. toxic role in relevance to Parkinson's disease.
越来越多的证据表明α-突触核蛋白在神经元中的核定位与其一级序列/结构组织密切相关，这促使我们研究其 DNA 结合能力。随后，我们首次证明了 DNA 与α-突触核蛋白的相互作用，这一结果也得到了其他人的证实。我们最近还表明，双链寡核苷酸诱导α-突触核蛋白部分折叠并促进其聚集，而单链环状 DNA 和超螺旋质粒 DNA 诱导形成富含螺旋的构象，并防止蛋白发生纤维状聚集。反过来，α-突触核蛋白可将 DNA 构象从 B 型转变为一种改变的 B 型，这可能会影响 DNA 转录。有趣的是，与阿尔茨海默病和朊病毒病分别相关的淀粉样β肽和朊病毒蛋白也被证明具有 DNA 结合活性，这表明 DNA 结合可能是与各种神经退行性疾病相关的许多淀粉样蛋白的共同特性。在这篇综述中，我们讨论了 DNA- α-突触核蛋白相互作用的生物学意义；它在帕金森病中的有益和有害作用。
