title: Volumetric contributions of loop regions of G-quadruplex DNA to the formation of the tertiary structure.
abstract: DNA guanine-quadruplexes (G-quadruplexes) are unique DNA structures formed by guanine-rich sequences. The loop regions of G-quadruplexes play key roles in stability and topology of G-quadruplexes. Here, we investigated volumetric changes induced by pressure in the folding of the G-quadruplex formed by the thrombin binding aptamer (TBA) with mutations within the loop regions. The change of partial molar volume in the transition from coil to G-quadruplex, ∆Vtr, of TBA with a mutation from T to A in the 5' most loop (TBA T3A) was 75.5cm3mol-1, which was larger than that of TBA (54.6cm3mol-1). TBA with a G to T mutation in the central loop (TBA G8T) had thermal stability similar to TBA T3A but a smaller ∆Vtrof 41.1cm3mol-1. In the presence of poly(ethylene)glycol 200 (PEG200), ∆Vtrvalues were 14.7cm3mol-1for TBA T3A and 13.2cm3mol-1for TBA G8T. These results suggest that the two mutations destabilize the G-quadruplex structure differently. Thus, volumetric data obtained using pressure-based thermodynamic analyses provides information about the dynamics of the loop regions and the roles of loops in the stabilities and folding of G-quadruplex structures.
authors.affiliation: FIBER (Frontier Institute for Biomolecular Engineering Research), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: FIBER (Frontier Institute for Biomolecular Engineering Research), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan; FIRST (Graduate School of Frontiers of Innovative Research in Science and Technology), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: sugimoto@konan-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation / Q000528:radiation effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D013816:Thermodynamics; D044366:Transition Temperature; D014466:Ultraviolet Rays
chemical_list: D011092:Polyethylene Glycols; D004247:DNA
keywords: DNA G-quadruplex; Loop; Pressure; Thermodynamics; Volume