Department of Chemistry, University of California Riverside, Riverside, California 92521-0403, United States.
J Proteome Res. 2021 Nov 5;20(11):4919-4924. doi: 10.1021/acs.jproteome.1c00603. Epub 2021 Sep 27.
DNA sequences of high guanine (G) content have the potential to form G quadruplex (G4) structures. A more complete understanding about the biological functions of G4 DNA requires the investigation about how these structures are recognized by proteins. Here, we conducted exhaustive quantitative proteomic experiments to profile the interaction proteomes of G4 structures by employing different sequences of G4 DNA derived from the human telomere and the promoters of c- and c- genes. Our results led to the identification of a number of candidate G4-interacting proteins, many of which were discovered here for the first time. These included three proteins that can bind to all three DNA G4 structures and 78 other proteins that can bind selectively to one or two of the three DNA G4 structure(s). We also validated that GRSF1 can bind directly and selectively toward G4 structure derived from the c- promoter. Our quantitative proteomic screening also led to the identification of a number of candidate "antireader" proteins of G4 DNA. Together, we uncovered a number of cellular proteins that exhibit general and selective recognitions of G4 folding patterns, which underscore the complexity of G4 DNA in biology and the importance of understanding fully the G4-interaction proteome.
富含鸟嘌呤（G）的 DNA 序列具有形成 G-四链体（G4）结构的潜力。为了更全面地了解 G4 DNA 的生物学功能，需要研究这些结构是如何被蛋白质识别的。在这里，我们通过使用源自人端粒和 c-和 c-基因启动子的不同 G4 DNA 序列，进行了详尽的定量蛋白质组学实验，以描绘 G4 结构的相互作用蛋白质组。我们的研究结果确定了一些候选的 G4 相互作用蛋白，其中许多是首次发现的。这些蛋白包括可以结合三种 DNA G4 结构的三种蛋白，以及可以选择性结合三种 DNA G4 结构之一或两种的 78 种其他蛋白。我们还验证了 GRSF1 可以直接和选择性地结合源自 c-启动子的 G4 结构。我们的定量蛋白质组学筛选还鉴定了一些候选的 G4 DNA“反读蛋白”。总的来说，我们发现了一些细胞蛋白，它们对 G4 折叠模式具有普遍和选择性的识别，这突显了 G4 DNA 在生物学中的复杂性，以及充分了解 G4 相互作用蛋白质组的重要性。
