title: Involvement of Long-Lived Intermediate States in the Complex Folding Pathway of the Human Telomeric G-Quadruplex.
abstract: The energy landscapes of human telomeric G-quadruplexes are complex, and their folding pathways have remained largely unexplored. By using real-time NMR spectroscopy, we investigated the K(+)-induced folding of the human telomeric DNA sequence 5'-TTGGG(TTAGGG)3 A-3'. Three long-lived states were detected during folding: a major conformation (hybrid-1), a previously structurally uncharacterized minor conformation (hybrid-2), and a partially unfolded state. The minor hybrid-2 conformation is formed faster than the more stable hybrid-1 conformation. Equilibration of the two states is slow and proceeds via a partially unfolded intermediate state, which can be described as an ensemble of hairpin-like structures.
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt/Main, Institution Max-von-Laue-Strasse 7, 60438 Frankfurt (Germany) http://schwalbe.org.chemie.uni-frankfurt.de.
authors.forename: Irene
authors.initials: I
authors.lastname: Bessi
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt/Main, Institution Max-von-Laue-Strasse 7, 60438 Frankfurt (Germany) http://schwalbe.org.chemie.uni-frankfurt.de.
authors.forename: Hendrik R A
authors.initials: HR
authors.lastname: Jonker
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt/Main, Institution Max-von-Laue-Strasse 7, 60438 Frankfurt (Germany) http://schwalbe.org.chemie.uni-frankfurt.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt/Main, Institution Max-von-Laue-Strasse 7, 60438 Frankfurt (Germany) http://schwalbe.org.chemie.uni-frankfurt.de. schwalbe@nmr.uni-frankfurt.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D016615:Telomere / Q000737:chemistry*
chemical_list: D004247:DNA
keywords: DNA structures; G-quadruplexes; conformation analysis; folding kinetics; real-time NMR spectroscopy