Informace o publikaci

Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label

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ZHANG Xiaojun XU Cui-Xia DI FELICE Rosa ŠPONER Jiří ISLAM Barira STADLBAUER Petr DING Yuan MAO Lingling MAO Zong-Wan QIN Peter Z.

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj Biochemistry
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5b01189
Doi http://dx.doi.org/10.1021/acs.biochem.5b01189
Obor Biochemie
Klíčová slova PARAMAGNETIC-RESONANCE SPECTROSCOPY; AMBER FORCE-FIELD; NUCLEIC-ACIDS; K+ SOLUTION; NANOMETER DISTANCES; CIRCULAR-DICHROISM; DNA DUPLEX; SEQUENCE; RNA; SIMULATIONS
Popis Guanine-rich oligonucleotides can form a unique G-quadruplex (GQ) structure with stacking units of four guanine bases organized in a plane through Hoogsteen bonding. GQ structures have been detected in vivo and shown to exert their roles in maintaining genome integrity and regulating gene expression. Understanding GQ conformation is important for understanding its inherent biological role and for devising strategies to control and manipulate functions based on targeting GQ. Although a number of biophysical methods have been used to investigate structure and dynamics of GQs, our understanding is far from complete. As such, this work explores the use of the site-directed spin labeling technique, complemented by molecular dynamics simulations, for investigating GQ conformations. A nucleotide-independent nitroxide label (R5), which has been previously applied for probing conformations of noncoding RNA and DNA duplexes, is attached to multiple sites in a 22-nucleotide DNA strand derived from the human telomeric sequence (hTel-22) that is known to form GQ. The R5 labels are shown to minimally impact GQ folding, and inter-R5 distances measured using double electron-electron resonance spectroscopy are shown to adequately distinguish the different topological conformations of hTel-22 and report variations in their occupancies in response to changes of the environment variables such as salt, crowding agent, and small molecule ligand. The work demonstrates that the R5 label is able to probe GQ conformation and establishes the base for using R5 to study more complex sequences, such as those that may potentially form multimeric GQs in long telomeric repeats.
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