title: Folding dynamics and conformational heterogeneity of human telomeric G-quadruplex structures in Na+ solutions by single molecule FRET microscopy.
abstract: G-quadruplex structures can occur throughout the genome, including at telomeres. They are involved in cellular regulation and are potential drug targets. Human telomeric G-quadruplex structures can fold into a number of different conformations and show large conformational diversity. To elucidate the different G-quadruplex conformations and their dynamics, we investigated telomeric G-quadruplex folding using single molecule FRET microscopy in conditions where it was previously believed to yield low structural heterogeneity. We observed four FRET states in Na(+) buffers: an unfolded state and three G-quadruplex related states that can interconvert between each other. Several of these states were almost equally populated at low to medium salt concentrations. These observations appear surprising as previous studies reported primarily one G-quadruplex conformation in Na(+) buffers. Our results permit, through the analysis of the dynamics of the different observed states, the identification of a more stable G-quadruplex conformation and two transient G-quadruplex states. Importantly these results offer a unique view into G-quadruplex topological heterogeneity and conformational dynamics.
authors.affiliation: Interdisciplinary Nanoscience center (iNANO), Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Sofie L
authors.initials: SL
authors.lastname: Noer
authors.affiliation: Interdisciplinary Nanoscience center (iNANO), Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Preus
authors.affiliation: Interdisciplinary Nanoscience center (iNANO), Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gudnason
authors.affiliation: Interdisciplinary Nanoscience center (iNANO), Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Mikayel
authors.initials: M
authors.lastname: Aznauryan
authors.affiliation: University of Bordeaux, ARNA Lab, IECB, 33076 Bordeaux, France INSERM, U1212, IECB, 33607 Pessac, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
authors.affiliation: Interdisciplinary Nanoscience center (iNANO), Aarhus University, 8000 Aarhus, Denmark vicb@inano.au.dk.
authors.forename: Victoria
authors.initials: V
authors.lastname: Birkedal
mesh_terms: D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008853:Microscopy; D009690:Nucleic Acid Conformation; D012091:Repetitive Sequences, Nucleic Acid; D012964:Sodium / Q000737:chemistry*; D012996:Solutions; D016615:Telomere / Q000737:chemistry* / Q000235:genetics
chemical_list: D012996:Solutions; D012964:Sodium