School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore; Laboratoire de Biologie et de Pharmacologie Appliquée, CNRS UMR 8113, Ecole Normale Supérieure Paris-Saclay, 61 Avenue du président Wilson, Cachan 94235, France.
School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
J Struct Biol. 2020 Jan 1;209(1):107399. doi: 10.1016/j.jsb.2019.10.001. Epub 2019 Oct 3.
G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3'-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5'-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads.
四链体（G4）是核酸的二级结构，可以在细胞中形成，具有多种生物学功能。几种具有生物学重要性的蛋白质与四链体相互作用，其中 RHAU（或 DHX36）——一种来自 DEAH 盒超家族的解旋酶，被证明能够有效地结合和解旋四链体。我们报告了 RHAU 的 N 端片段与平行链 G-四链体暴露的四联体结合的 1.5Å 分辨率的 X 射线共晶结构。RHAU 肽折叠成 L 形α螺旋，并通过π堆积和静电相互作用与四链体结合。我们的复合物的 X 射线晶体结构确定了关键的氨基酸残基，这些残基对于 3'-端 G•G•G•G 四联体的四链体-肽结合相互作用很重要。结合以前 RHAU 与 5'-端 G•G•G•G 和 G•G•A•T 四联体结合的溶液和晶体结构，我们的晶体结构突出了 RHAU 中存在一个强大的四链体识别基序，它可以适应不同的可及四联体。
