Structure of a DNA G-Quadruplex Related to Osteoporosis with a
G-A Bulge Forming a Pseudo-loop

J 2020

Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop

LENARČIČ ŽIVKOVIĆ, Martina, J. ROZMAN and J. PLAVEC

Basic information

Original name

Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop

Authors

LENARČIČ ŽIVKOVIĆ, Martina (705 Slovenia, guarantor, belonging to the institution), J. ROZMAN and J. PLAVEC

Edition

MOLECULES, Orlando, Florida, Academic Press, 2020, 1420-3049

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.411

RIV identification code

RIV/00216224:14740/20:00118353

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/molecules25204867

UT WoS

000585504400001

Keywords in English

G-quadruplex; NMR spectroscopy; structure; osteoporosis

Abstract

V originále

Bone remodeling is a fine-tuned process principally regulated by a cascade triggered by interaction of receptor activator of NF-kappa B (RANK) and RANK ligand (RANKL). Excessive activity of the RANKL gene leads to increased bone resorption and can influence the incidence of osteoporosis. Although much has been learned about the intracellular signals activated by RANKL/RANK complex, significantly less is known about the molecular mechanisms of regulation of RANKL expression. Here, we report on the structure of an unprecedented DNA G-quadruplex, well-known secondary structure-mediated gene expression regulator, formed by a G-rich sequence found in the regulatory region of a RANKL gene. Solution-state NMR structural study reveals the formation of a three-layered parallel-type G-quadruplex characterized by an unique features, including a G-A bulge. Although a guanine within a G-tract occupies syn glycosidic conformation, bulge-forming residues arrange in a pseudo-loop conformation to facilitate partial 5/6-ring stacking, typical of G-quadruplex structures with parallel G-tracts orientation. Such distinctive structural features protruding from the core of the structure can represent a novel platform for design of highly specific ligands with anti-osteoporotic function. Additionally, our study suggests that the expression of RANKL gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).

Citovat

LENARČIČ ŽIVKOVIĆ, Martina, J. ROZMAN and J. PLAVEC. Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop. MOLECULES. Orlando, Florida: Academic Press, 2020, vol. 25, No 20, p. 4867-4882. ISSN 1420-3049. Available from: https://dx.doi.org/10.3390/molecules25204867.

@article{1750656,
   author = {Lenarčič Živković, Martina and Rozman, J. and Plavec, J.},
   article_location = {Orlando, Florida},
   article_number = {20},
   doi = {http://dx.doi.org/10.3390/molecules25204867},
   keywords = {G-quadruplex; NMR spectroscopy; structure; osteoporosis},
   language = {eng},
   issn = {1420-3049},
   journal = {MOLECULES},
   title = {Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop},
   url = {https://www.mdpi.com/1420-3049/25/20/4867},
   volume = {25},
   year = {2020}
}

TY  - JOUR
ID  - 1750656
AU  - Lenarčič Živković, Martina - Rozman, J. - Plavec, J.
PY  - 2020
TI  - Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop
JF  - MOLECULES
VL  - 25
IS  - 20
SP  - 4867
EP  - 4867
PB  - Academic Press
SN  - 14203049
KW  - G-quadruplex
KW  - NMR spectroscopy
KW  - structure
KW  - osteoporosis
UR  - https://www.mdpi.com/1420-3049/25/20/4867
N2  - Bone remodeling is a fine-tuned process principally regulated by a cascade triggered by interaction of receptor activator of NF-kappa B (RANK) and RANK ligand (RANKL). Excessive activity of the RANKL gene leads to increased bone resorption and can influence the incidence of osteoporosis. Although much has been learned about the intracellular signals activated by RANKL/RANK complex, significantly less is known about the molecular mechanisms of regulation of RANKL expression. Here, we report on the structure of an unprecedented DNA G-quadruplex, well-known secondary structure-mediated gene expression regulator, formed by a G-rich sequence found in the regulatory region of a RANKL gene. Solution-state NMR structural study reveals the formation of a three-layered parallel-type G-quadruplex characterized by an unique features, including a G-A bulge. Although a guanine within a G-tract occupies syn glycosidic conformation, bulge-forming residues arrange in a pseudo-loop conformation to facilitate partial 5/6-ring stacking, typical of G-quadruplex structures with parallel G-tracts orientation. Such distinctive structural features protruding from the core of the structure can represent a novel platform for design of highly specific ligands with anti-osteoporotic function. Additionally, our study suggests that the expression of RANKL gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).
ER  -

LENARČIČ ŽIVKOVI$\backslash$'C, Martina, J. ROZMAN and J. PLAVEC. Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop. \textit{MOLECULES}. Orlando, Florida: Academic Press, 2020, vol.~25, No~20, p.~4867-4882. ISSN~1420-3049. Available from: https://dx.doi.org/10.3390/molecules25204867.

Detailed Information on Publication Record