title: Confined space facilitates G-quadruplex formation.
abstract: Molecular simulations suggest that the stability of a folded macromolecule increases in a confined space due to entropic effects. However, due to the interactions between the confined molecular structure and the walls of the container, clear-cut experimental evidence for this prediction is lacking. Here, using DNA origami nanocages, we show the pure effect of confined space on the property of individual human telomeric DNA G-quadruplexes. We induce targeted mechanical unfolding of the G-quadruplex while leaving the nanocage unperturbed. We find that the mechanical and thermodynamic stabilities of the G-quadruplex inside the nanocage increase with decreasing cage size. Compared to the case of diluted or molecularly crowded buffer solutions, the G-quadruplex inside the nanocage is significantly more stable, showing a 100 times faster folding rate. Our findings suggest the possibility of co-replicational or co-transcriptional folding of G-quadruplex inside the polymerase machinery in cells.
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, USA.
authors.forename: Sagun
authors.initials: S
authors.lastname: Jonchhe
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Emura
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Hidaka
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Endo
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, USA.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Mao
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D049329:Nanostructures / Q000737:chemistry*
chemical_list: D004247:DNA