DSSR-enabled G4 identification/annotation: PDB entry 6zrm
Summary information and primary citation
- PDB-id
- 6zrm
- Class
- DNA
- Method
- NMR
- Summary
- G-quadruplex with a g-a bulge
- Reference
- Lenarcic Zivkovic M, Rozman J, Plavec J (2020): "Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop ." Molecules, 25. doi: 10.3390/molecules25204867.
- 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 <i>RANKL</i> 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 <i>RANKL</i> 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 <i>RANKL</i> 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 <i>syn</i> glycosidic conformation, bulge-forming residues arrange in a <i>pseudo-loop</i> 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 <i>RANKL</i> gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.262 type=other O+ nts=4 GGGG A.DG2,A.DG6,A.DG12,A.DG18 2 glyco-bond=---- sugar=---- groove=---- planarity=0.185 type=other O+ nts=4 GGGG A.DG3,A.DG7,A.DG13,A.DG19 3 glyco-bond=--s- sugar=--.- groove=-wn- planarity=0.138 type=planar O+ nts=4 GGGG A.DG4,A.DG8,A.DG16,A.DG20
List of 1 G4-helix
In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.
Helix#1, 3 G-tetrads, INTRA-molecular, with 1 stem
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG12,A.DG18 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG13,A.DG19 3 glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG16,A.DG20 step#1 pm(>>,forward) area=14.82 rise=3.47 twist=23.0 step#2 pm(>>,forward) area=9.11 rise=3.39 twist=29.9 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG6,A.DG7,A.DG8 strand#3 DNA glyco-bond=--s sugar=--. nts=3 GGG A.DG12,A.DG13,A.DG16 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG18,A.DG19,A.DG20 |
| 2 stacking diagrams | |
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG12,A.DG18 |
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2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG13,A.DG19 |
List of 1 G4-stem
In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.
Stem#1, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG12,A.DG18 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG13,A.DG19 3 glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG16,A.DG20 step#1 pm(>>,forward) area=14.82 rise=3.47 twist=23.0 step#2 pm(>>,forward) area=9.11 rise=3.39 twist=29.9 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG6,A.DG7,A.DG8 strand#3* U DNA glyco-bond=--s sugar=--. nts=3 GGG A.DG12,A.DG13,A.DG16 bulged-nts=2 GA A.DG14,A.DA15 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG18,A.DG19,A.DG20 loop#1 type=propeller strands=[#1,#2] nts=1 A A.DA5 loop#2 type=propeller strands=[#2,#3] nts=3 AGC A.DA9,A.DG10,A.DC11 loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT17 |