Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex
Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex
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DOI：
10.1073/pnas.1422605112
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发表时间：
2015-08-04
影响因子：
11.1
通讯作者：
Anh Tuan Phan
中科院分区：
文献类型：
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作者：
Heddi, Brahim;Cheong, Vee Vee;Anh Tuan Phan
被称为G-四链体的四链核酸结构与重要的细胞过程相关，这些过程应该需要G-四链体-蛋白质相互作用。然而，特异性G-四链体识别蛋白质的结构基础尚未被理解。与富含AU的元件（RHAU）相关的DEAH（Asp-Glu-Ala-His）盒RNA解旋酶（也称为DHX 36或G4 R1）特异性结合并解析平行链的G-四链体。在这里，我们确定了一个18个氨基酸的G-四链体结合结构域的RHAU，并确定了这种肽结合到一个平行的DNA G-四链体的结构。我们的结构解释了RHAU如何特异性地识别平行的G-四链体。该肽覆盖末端鸟嘌呤碱基四联体（G-四联体），并使用三个带正电荷的氨基酸和带负电荷的磷酸基团之间的三锚点静电相互作用来夹持G-四联体。这种结合模式与选择用于特异性G-四链体靶向的大多数配体的结合模式惊人地相似。与暴露的G-四联体结合代表了特异性靶向G-四联体结构的简单而有效的方式。
Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.