DSSR-enabled G4 identification/annotation: PDB entry 8rzx
Summary information and primary citation
- PDB-id
- 8rzx
- Class
- DNA
- Method
- NMR
- Summary
- Solution structure of a parallel stranded g-quadruplex formed in orai1 promoter
- Reference
- Chatterjee O, Jana J, Panda S, Dutta A, Sharma A, Saurav S, Motiani RK, Weisz K, Chatterjee S (2024): "Remodeling Ca 2+ dynamics by targeting a promising E-box containing G-quadruplex at ORAI1 promoter in triple-negative breast cancer." Cell Calcium, 123, 102944. doi: 10.1016/j.ceca.2024.102944.
- Abstract
- ORAI1 is an intrinsic component of store-operated calcium entry (SOCE) that strictly regulates Ca<sub>2+</sub> influx in most non-excitable cells. ORAI1 is overexpressed in a wide variety of cancers, and its signal transduction has been associated with chemotherapy resistance. There is extensive proteomic interaction of ORAI1 with other channels and effectors, resulting in various altered phenotypes. However, the transcription regulation of ORAI1 is not well understood. We have found a putative G-quadruplex (G4) motif, ORAI1-Pu, in the upstream promoter region of the gene, having regulatory functions. High-resolution 3-D NMR structure elucidation suggests that ORAI1-Pu is a stable parallel-stranded G4, having a long 8-nt loop imparting dynamics without affecting the structural stability. The protruded loop further houses an E-box motif that provides a docking site for transcription factors like Zeb1. The G4 structure was also endogenously observed using Chromatin Immunoprecipitation (ChIP) with anti-G4 antibody (BG4) in the MDA-MB-231 cell line overexpressing ORAI1. Ligand-mediated stabilization suggested that the stabilized G4 represses transcription in cancer cell line MDA-MB-231. Downregulation of transcription further led to decreased Ca<sub>2+</sub> entry by the SOCE pathway, as observed by live-cell Fura-2 Ca<sub>2+</sub> imaging.
- 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=0.128 type=planar O+ nts=4 GGGG A.DG2,A.DG6,A.DG17,A.DG21 2 glyco-bond=---- sugar=---- groove=---- planarity=0.218 type=other O+ nts=4 GGGG A.DG3,A.DG7,A.DG18,A.DG22 3 glyco-bond=---- sugar=---- groove=---- planarity=0.336 type=other O+ nts=4 GGGG A.DG4,A.DG8,A.DG19,A.DG23
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.DG17,A.DG21 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG18,A.DG22 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG19,A.DG23 step#1 pm(>>,forward) area=8.19 rise=3.39 twist=34.2 step#2 pm(>>,forward) area=17.75 rise=3.40 twist=20.4 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=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG21,A.DG22,A.DG23 |
| 2 stacking diagrams | |
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG17,A.DG21 |
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2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG18,A.DG22 |
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)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG17,A.DG21 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG18,A.DG22 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG19,A.DG23 step#1 pm(>>,forward) area=8.19 rise=3.39 twist=34.2 step#2 pm(>>,forward) area=17.75 rise=3.40 twist=20.4 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=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG21,A.DG22,A.DG23 loop#1 type=propeller strands=[#1,#2] nts=1 C A.DC5 loop#2 type=propeller strands=[#2,#3] nts=8 GCACAGGT A.DG9,A.DC10,A.DA11,A.DC12,A.DA13,A.DG14,A.DG15,A.DT16 loop#3 type=propeller strands=[#3,#4] nts=1 C A.DC20 |