Revealing structural peculiarities of homopurine GA repetition
stuck by i-motif clip

J 2021

Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip

NOVOTNÝ, Aleš, Jan NOVOTNÝ, Iva KEJNOVSKÁ, Michaela VORLÍČKOVÁ, Radovan FIALA et. al.

Basic information

Original name

Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip

Authors

NOVOTNÝ, Aleš (203 Czech Republic, belonging to the institution), Jan NOVOTNÝ (203 Czech Republic, belonging to the institution), Iva KEJNOVSKÁ (203 Czech Republic), Michaela VORLÍČKOVÁ (203 Czech Republic), Radovan FIALA (203 Czech Republic, belonging to the institution) and Radek MAREK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Nucleic Acids Research, Oxford, Oxford University Press, 2021, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

DOI: 10.1093/nar/gkab915

Impact factor

Impact factor: 19.160

RIV identification code

RIV/00216224:14740/21:00122684

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/nar/gkab915

UT WoS

000728384400008

Keywords in English

DNA; i-motif; duplex; NMR spectroscopy; CD; molecular dynamics

Abstract

V originále

Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C3 clip is analyzed by NMR and CD spectroscopies to understand the sequence–structure–stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C3 clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C3GAGA and methylated GAGAC3 exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids.

Links

EF16_013/0001776, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii pro lidské zdraví

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

NOVOTNÝ, Aleš, Jan NOVOTNÝ, Iva KEJNOVSKÁ, Michaela VORLÍČKOVÁ, Radovan FIALA and Radek MAREK. Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip. Nucleic Acids Research. Oxford: Oxford University Press, 2021, vol. 49, No 20, p. 11425-11437. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkab915.

@article{1800082,
   author = {Novotný, Aleš and Novotný, Jan and Kejnovská, Iva and Vorlíčková, Michaela and Fiala, Radovan and Marek, Radek},
   article_location = {Oxford},
   article_number = {20},
   doi = {http://dx.doi.org/10.1093/nar/gkab915},
   keywords = {DNA; i-motif; duplex; NMR spectroscopy; CD; molecular dynamics},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip},
   url = {http://dx.doi.org/10.1093/nar/gkab915},
   volume = {49},
   year = {2021}
}

TY  - JOUR
ID  - 1800082
AU  - Novotný, Aleš - Novotný, Jan - Kejnovská, Iva - Vorlíčková, Michaela - Fiala, Radovan - Marek, Radek
PY  - 2021
TI  - Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip
JF  - Nucleic Acids Research
VL  - 49
IS  - 20
SP  - 11425-11437
EP  - 11425-11437
PB  - Oxford University Press
SN  - 03051048
KW  - DNA
KW  - i-motif
KW  - duplex
KW  - NMR spectroscopy
KW  - CD
KW  - molecular dynamics
UR  - http://dx.doi.org/10.1093/nar/gkab915
N2  - Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C3 clip is analyzed by NMR and CD spectroscopies to understand the sequence–structure–stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C3 clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C3GAGA and methylated GAGAC3 exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids.
ER  -

NOVOTNÝ, Aleš, Jan NOVOTNÝ, Iva KEJNOVSKÁ, Michaela VORLÍČKOVÁ, Radovan FIALA and Radek MAREK. Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2021, vol.~49, No~20, p.~11425-11437. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkab915.

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