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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00118353" target="_blank" >RIV/00216224:14740/20:00118353 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1420-3049/25/20/4867" target="_blank" >https://www.mdpi.com/1420-3049/25/20/4867</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules25204867" target="_blank" >10.3390/molecules25204867</a>

Result language

angličtina

Original language name

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

Original language description

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).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

MOLECULES

ISSN

1420-3049

e-ISSN

—

Volume of the periodical

25

Issue of the periodical within the volume

20

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

4867

UT code for WoS article

000585504400001

EID of the result in the Scopus database

2-s2.0-85093647689