title: Loop lengths of G-quadruplex structures affect the G-quadruplex DNA binding selectivity of the RGG motif in Ewing's sarcoma.
abstract: The G-quadruplex nucleic acid structural motif is a target for designing molecules with potential anticancer properties. To achieve therapeutic selectivity by targeting the G-quadruplex, the molecules must be able to differentiate between the DNA of different G-quadruplexes. We recently reported that the Arg-Gly-Gly repeat (RGG) of the C-terminus in Ewing's sarcoma protein (EWS), which is a group of dominant oncogenes that arise due to chromosomal translocations, is capable of binding to G-quadruplex telomere DNA and RNA via arginine residues and stabilize the G-quadruplex DNA form in vitro. Here, we show that the RGG of EWS binds preferentially to G-quadruplexes with longer loops, which is not related to the topology of the G-quadruplex structure. Moreover, the G-quadruplex DNA binding of the RGG in EWS depends on the phosphate backbone of the loops in the G-quadruplex DNA. We also investigated the G-quadruplex DNA binding activity of the N- and C-terminally truncated RGG to assess the role of the regions in the RGG in G-quadruplex DNA binding. Our findings indicate that the RGG and the other arginine-rich motif of residues 617-656 of the RGG in EWS are important for the specific binding to G-quadruplex DNA. These findings will contribute to the development of molecules that selectively target different G-quadruplex DNA.
authors.affiliation: Faculty of Science, Department of Chemistry, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahama
authors.forename: Chieri
authors.initials: C
authors.lastname: Sugimoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arai
authors.forename: Riki
authors.initials: R
authors.lastname: Kurokawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Oyoshi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D034802:RNA-Binding Protein EWS / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D034802:RNA-Binding Protein EWS; D004247:DNA; D001120:Arginine; D005982:Glutathione Transferase