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

J 2016

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

ZHANG, Xiaojun; Cui-Xia XU; Rosa DI FELICE; Jiří ŠPONER; Barira ISLAM et. al.

Basic information

Original name

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

Authors

ZHANG, Xiaojun (840 United States of America); Cui-Xia XU (156 China); Rosa DI FELICE (840 United States of America); Jiří ŠPONER (203 Czech Republic, guarantor, belonging to the institution); Barira ISLAM (356 India, belonging to the institution); Petr STADLBAUER (203 Czech Republic); Yuan DING (840 United States of America); Lingling MAO (840 United States of America); Zong-Wan MAO (156 China) and Peter Z. QIN (840 United States of America)

Edition

Biochemistry, WASHINGTON, AMER CHEMICAL SOC, 2016, 0006-2960

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 2.938

RIV identification code

RIV/00216224:14740/16:00089404

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1021/acs.biochem.5b01189

UT WoS

000368562100013

EID Scopus

2-s2.0-84955326510

Keywords in English

PARAMAGNETIC-RESONANCE SPECTROSCOPY; AMBER FORCE-FIELD; NUCLEIC-ACIDS; K+ SOLUTION; NANOMETER DISTANCES; CIRCULAR-DICHROISM; DNA DUPLEX; SEQUENCE; RNA; SIMULATIONS

Abstract

In the original language

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.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.30.0037, research and development project

Name: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce

Cite

ZHANG, Xiaojun; Cui-Xia XU; Rosa DI FELICE; Jiří ŠPONER; Barira ISLAM; Petr STADLBAUER; Yuan DING; Lingling MAO; Zong-Wan MAO and Peter Z. QIN. Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label. Biochemistry. WASHINGTON: AMER CHEMICAL SOC, 2016, vol. 55, No 2, p. 360-372. ISSN 0006-2960. Available from: https://doi.org/10.1021/acs.biochem.5b01189.

@article{1335878,
   author = {Zhang, Xiaojun and Xu, CuiandXia and Di Felice, Rosa and Šponer, Jiří and Islam, Barira and Stadlbauer, Petr and Ding, Yuan and Mao, Lingling and Mao, ZongandWan and Qin, Peter Z.},
   article_location = {WASHINGTON},
   article_number = {2},
   doi = {https://doi.org/10.1021/acs.biochem.5b01189},
   keywords = {PARAMAGNETIC-RESONANCE SPECTROSCOPY; AMBER FORCE-FIELD; NUCLEIC-ACIDS; K+ SOLUTION; NANOMETER DISTANCES; CIRCULAR-DICHROISM; DNA DUPLEX; SEQUENCE; RNA; SIMULATIONS},
   language = {eng},
   issn = {0006-2960},
   journal = {Biochemistry},
   title = {Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label},
   url = {http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5b01189},
   volume = {55},
   year = {2016}
}

TY  - JOUR
ID  - 1335878
AU  - Zhang, Xiaojun - Xu, Cui-Xia - Di Felice, Rosa - Šponer, Jiří - Islam, Barira - Stadlbauer, Petr - Ding, Yuan - Mao, Lingling - Mao, Zong-Wan - Qin, Peter Z.
PY  - 2016
TI  - Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label
JF  - Biochemistry
VL  - 55
IS  - 2
SP  - 360-372
EP  - 360-372
PB  - AMER CHEMICAL SOC
SN  - 00062960
KW  - PARAMAGNETIC-RESONANCE SPECTROSCOPY
KW  - AMBER FORCE-FIELD
KW  - NUCLEIC-ACIDS
KW  - K+ SOLUTION
KW  - NANOMETER DISTANCES
KW  - CIRCULAR-DICHROISM
KW  - DNA DUPLEX
KW  - SEQUENCE
KW  - RNA
KW  - SIMULATIONS
UR  - http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5b01189
L2  - http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5b01189
N2  - 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.
ER  -

ZHANG, Xiaojun; Cui-Xia XU; Rosa DI FELICE; Jiří ŠPONER; Barira ISLAM; Petr STADLBAUER; Yuan DING; Lingling MAO; Zong-Wan MAO and Peter Z. QIN. Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label. \textit{Biochemistry}. WASHINGTON: AMER CHEMICAL SOC, 2016, vol.~55, No~2, p.~360-372. ISSN~0006-2960. Available from: https://doi.org/10.1021/acs.biochem.5b01189.

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