title: High-resolution insight into G-overhang architecture.
abstract: NMR and fluorescence spectroscopy were used to address the effect of intracellular molecular crowding and related hydration on a model telomeric G-quadruplex (G4) DNA structure (d(AG(3)(TTAGGG)(3))). d(AG(3)(TTAGGG)(3)) prevalently adopted the hybrid-1 conformation in vivo, ex vivo, and in dilute potassium-based solution, while it formed the parallel propeller fold in water-depleted potassium-based solution, a commonly used model system for studying intracellular molecular crowding. The dilute potassium-based solution appeared to imitate the properties of the cellular environment required for d(AG(3)(TTAGGG)(3)) folding under in vivo and ex vivo conditions. High-resolution NMR investigations of site-specifically (15)N-labeled G4 units in native-like single-stranded telomeric DNA revealed that the 3'-terminal and internal G4 unit predominantly coexist in 2-tetrad antiparallel basket and hybrid-2 structures that are arranged in "beads-on-a-string"-like fashion. Our data provide the first high-resolution insight into the telomeric G-overhang architecture under essentially physiological conditions and identify the 2-tetrad antiparallel basket and hybrid-2 topologies as the structural targets for the development of telomere-specific G4 ligands.
authors: Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt/Main, Germany. rhaensel.bpc@gmail.com
authors: Robert
authors: R
authors: Hänsel
authors: Frank
authors: F
authors: Löhr
authors: Lukáš
authors: L
authors: Trantirek
authors: Volker
authors: V
authors: Dötsch
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D016615:Telomere / Q000737:chemistry*
chemical_list: D004247:DNA