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G-线、双分子和四分子四重链的形成:人SYTX基因富含G的DNA序列的阳离子诱导结构多晶型物。

Formation of G-wires, bimolecular and tetramolecular quadruplex: Cation-induced structural polymorphs of G-rich DNA sequence of human SYTX gene.

作者信息

Ahmed Saami, Kaushik Mahima, Chaudhary Swati, Kukreti Shrikant

机构信息

Nucleic Acids Research Lab, Department of Chemistry, University of Delhi, Delhi, 110007, India.

Cluster Innovation Centre, University of Delhi, Delhi, India.

出版信息

Biopolymers. 2018 May;109(5):e23115. doi: 10.1002/bip.23115. Epub 2018 Apr 19.

Abstract

An exceptional property of auto-folding into a range of intra- as well as intermolecular quadruplexes by guanine-rich oligomers (GROs) of promoters, telomeres and various other genomic locations is still one of the most attractive areas of research at present times. The main reason for this attention is due to their established in vivo existence and biological relevance. Herein, the structural status of a 20-nt long G-rich sequence with two G5 stretches (SG20) is investigated using various biophysical and biochemical techniques. Bioinformatics analysis suggested the presence of a 17-nt stretch of this SG20 sequence in the intronic region of human SYTX (Synaptotagmin 10) gene. The SYTX gene helps in sensing out the Ca ion, causing its intake in the pre-synaptic neuron. A range of various topologies like bimolecular, tetramolecular and guanine-wires (nano-wires) was exhibited by the studied sequence, as a function of cations (Na /K ) concentration. UV-thermal denaturation, gel electrophoresis, and circular dichroism (CD) spectroscopy showed correlations and established a cation-dependent structural switch. The G-wire formation, in the presence of K , may further be explored for its possible relevance in nano-biotechnological applications.

摘要

启动子、端粒及其他各种基因组位置富含鸟嘌呤的寡聚物(GROs)自动折叠成一系列分子内和分子间四链体的特殊性质,仍是当前最具吸引力的研究领域之一。受到关注的主要原因是它们在体内确实存在且具有生物学相关性。在此,使用各种生物物理和生化技术研究了具有两个G5片段(SG20)的20个核苷酸长的富含G序列的结构状态。生物信息学分析表明,该SG20序列在人类SYTX(突触结合蛋白10)基因的内含子区域存在一段17个核苷酸的片段。SYTX基因有助于感知钙离子,使其进入突触前神经元。所研究的序列表现出一系列不同的拓扑结构,如双分子、四分子和鸟嘌呤链(纳米链),这是阳离子(Na⁺/K⁺)浓度的函数。紫外热变性、凝胶电泳和圆二色(CD)光谱显示出相关性,并确定了阳离子依赖性结构转换。在钾离子存在下形成的鸟嘌呤链,其在纳米生物技术应用中的潜在相关性可能值得进一步探索。

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