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

LENARČIČ ŽIVKOVIĆ, Martina, J. ROZMAN a 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, roč. 25, č. 20, s. 4867-4882. ISSN 1420-3049. Dostupné z: https://dx.doi.org/10.3390/molecules25204867.

Základní údaje

• Originální název: Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop
• Autoři: LENARČIČ ŽIVKOVIĆ, Martina (705 Slovinsko, garant, domácí), J. ROZMAN a J. PLAVEC.
• Vydání: MOLECULES, Orlando, Florida, Academic Press, 2020, 1420-3049.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10608 Biochemistry and molecular biology
• Stát vydavatele: Švýcarsko
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 4.411
• Kód RIV: RIV/00216224:14740/20:00118353
• Organizační jednotka: Středoevropský technologický institut
• Doi: http://dx.doi.org/10.3390/molecules25204867
• UT WoS: 000585504400001
• Klíčová slova anglicky: G-quadruplex; NMR spectroscopy; structure; osteoporosis
• Štítky: rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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).