Quadruplexes in 'Dicty': crystal structure of a four-quartet G-quadruplex formed by G-rich motif found in the Dictyostelium discoideum genome.
Quadruplexes in 'Dicty': crystal structure of a four-quartet G-quadruplex formed by G-rich motif found in the Dictyostelium discoideum genome.
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DOI：
10.1093/nar/gky290
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发表时间：
2018-06-01
影响因子：
14.9
通讯作者：
Yatsunyk LA
中科院分区：
文献类型：
--
作者：
Guédin A;Lin LY;Armane S;Lacroix L;Mergny JL;Thore S;Yatsunyk LA
富含鸟嘌呤的DNA有可能折叠成非典型的G-四链体（G4）结构。社会阿米巴Dictyosteelicdiscoideum的基因组分析表明，具有G4形成潜力的序列数量很少（249-1055）。因此，D.盘突藻是研究G4的存在与其生物学功能之间关系的理想模式生物。作为本研究的第一步，我们从D.盘状突根据晶体结构，该序列折叠成具有两个横向环和一个对角环的四重四重分子内反平行G4。G-四链体核心通过G-C Watson-Crick碱基对和A-T-A三联体进一步稳定，并显示出高热稳定性（在100 mM KCl下Tm > 90°C）。天然序列和环突变体的生物物理表征表明，DNA在溶液中和结晶形式中采用相同的结构，并且环相互作用对G4稳定性很重要，但对其折叠不重要。四分体G4结构稀疏。因此，我们的工作推进了对G-四链体结构多样性的理解，并为计算机药物筛选程序和G4预测工具提供了坐标。
Guanine-rich DNA has the potential to fold into non-canonical G-quadruplex (G4) structures. Analysis of the genome of the social amoeba Dictyostelium discoideum indicates a low number of sequences with G4-forming potential (249–1055). Therefore, D. discoideum is a perfect model organism to investigate the relationship between the presence of G4s and their biological functions. As a first step in this investigation, we crystallized the dGGGGGAGGGGTACAGGGGTACAGGGG sequence from the putative promoter region of two divergent genes in D. discoideum. According to the crystal structure, this sequence folds into a four-quartet intramolecular antiparallel G4 with two lateral and one diagonal loops. The G-quadruplex core is further stabilized by a G-C Watson–Crick base pair and a A–T–A triad and displays high thermal stability (Tm > 90°C at 100 mM KCl). Biophysical characterization of the native sequence and loop mutants suggests that the DNA adopts the same structure in solution and in crystalline form, and that loop interactions are important for the G4 stability but not for its folding. Four-tetrad G4 structures are sparse. Thus, our work advances understanding of the structural diversity of G-quadruplexes and yields coordinates for in silico drug screening programs and G4 predictive tools.
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DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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DOI：
10.1073/pnas.1418718112
发表时间：
2015-03-03
影响因子：
11.1
作者：
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影响因子：
16.8
作者：
Anh Tuan Phan;Kuryavyi, Vitaly;Darnell, Jennifer C.;Serganov, Alexander;Majumdar, Ananya;Ilin, Serge;Raslin, Tanya;Polonskaia, Anna;Chen, Cynthia;Clain, David;Darnell, Robert B.;Patel, Dinshaw J.
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