6ZRM

G-quadruplex with a G-A bulge

6ZRM の概要

• エントリーDOI: 10.2210/pdb6zrm/pdb
• NMR情報: BMRB: 34529
• 分子名称: DNA (5'-D(*TP*GP*GP*GP*AP*GP*GP*GP*AP*GP*CP*GP*GP*GP*AP*GP*TP*GP*GP*G)-3') (1 entity in total)
• 機能のキーワード: g-quadruplex structure bulge osteoporosis, dna
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6401.11

構造登録者

Lenarcic Zivkovic, M.,Plavec, J. (登録日: 2020-07-13, 公開日: 2021-05-26, 最終更新日: 2024-05-15)

主引用文献

Lenarcic Zivkovic, M.,Rozman, J.,Plavec, J.
Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop .
Molecules, 25:-, 2020

PubMed Abstract: Bone remodeling is a fine-tuned process principally regulated by a cascade triggered by interaction of receptor activator of NF-κB (RANK) and RANK ligand (RANKL). Excessive activity of the 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 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 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 glycosidic conformation, bulge-forming residues arrange in a 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 gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).

PubMed: 33096904
DOI: 10.3390/molecules25204867

実験手法

SOLUTION NMR