8RZX

Solution structure of a parallel stranded G-quadruplex formed in ORAI1 promoter

Summary for 8RZX

• Entry DOI: 10.2210/pdb8rzx/pdb
• NMR Information: BMRB: 34898
• Descriptor: DNA (5'-D(*TP*GP*GP*GP*CP*GP*GP*GP*GP*CP*AP*CP*AP*GP*GP*TP*GP*GP*GP*CP*GP*GP*GP*G)-3') (1 entity in total)
• Functional Keywords: g-quadruplex, parallel topology, orai1, long loop, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 7613.86

Authors

Jana, J.,Weisz, K. (deposition date: 2024-02-13, release date: 2024-08-21, Last modification date: 2024-09-11)

Primary citation

Chatterjee, O.,Jana, J.,Panda, S.,Dutta, A.,Sharma, A.,Saurav, S.,Motiani, R.K.,Weisz, K.,Chatterjee, S.
Remodeling Ca 2+ dynamics by targeting a promising E-box containing G-quadruplex at ORAI1 promoter in triple-negative breast cancer.
Cell Calcium, 123:102944-102944, 2024

PubMed Abstract: ORAI1 is an intrinsic component of store-operated calcium entry (SOCE) that strictly regulates Ca 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 entry by the SOCE pathway, as observed by live-cell Fura-2 Ca imaging.

PubMed: 39191092
DOI: 10.1016/j.ceca.2024.102944

Experimental method

SOLUTION NMR