title: A direct view of the complex multi-pathway folding of telomeric G-quadruplexes.
abstract: G-quadruplexes (G4s) are DNA secondary structures that are capable of forming and function in vivo The propensity of G4s to exhibit extreme polymorphism and complex dynamics is likely to influence their cellular function, yet a clear microscopic picture of their folding process is lacking. Here we employed single-molecule FRET microscopy to obtain a direct view of the folding and underlying conformational dynamics of G4s formed by the human telomeric sequence in potassium containing solutions. Our experiments allowed detecting several folded states that are populated in the course of G4 folding and determining their folding energetics and timescales. Combining the single-molecule data with molecular dynamics simulations enabled obtaining a structural description of the experimentally observed folded states. Our work thus provides a comprehensive thermodynamic and kinetic description of the folding of G4s that proceeds through a complex multi-route pathway, involving several marginally stable conformational states.
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.|Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
authors: Mikayel
authors: M
authors: Aznauryan
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.|Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
authors: Siri
authors: S
authors: Søndergaard
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
authors: Sofie L
authors: SL
authors: Noer
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.|Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
authors: Birgit
authors: B
authors: Schiøtt
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark vicb@inano.au.dk.|Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
authors: Victoria
authors: V
authors: Birkedal
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D009841:Oligonucleotides / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides; D011188:Potassium