bi1c00043_si_001.pdf (2.47 MB)
First Tandem Repeat of a Potassium Channel KCNN4 Minisatellite Folds into a V‑Loop G‑Quadruplex Structure
journal contributionposted on 2021-04-12, 17:08 authored by Yoanes Maria Vianney, Klaus Weisz
The KCNN4 gene encoding a potassium channel protein whose expression has been correlated with tumor progression was found to comprise a guanine-rich minisatellite region with the ability to form a putative G-quadruplex (G4). Given the suggested regulatory role of G4s in gene expression, G-quadruplex formation for the polymorphic first repeat of the minisatellite was studied by nuclear magnetic resonance spectroscopy. A stable G-quadruplex of a truncated mutant sequence was shown to represent one of several coexisting species of the wild-type sequence. The high-resolution structure features a noncanonical G4 with a broken G-column and a V-shaped loop. The presence of a 3′-flanking thymidine interacting with the lateral loop preceding the V loop seems to be critical for the formation of this G4 topology. On the contrary, an additional 5′-flanking residue disfavored but still allowed folding into the V-loop structure. The latter may therefore serve as a putative therapeutic target in strategies for G4-based modulation of KCNN4 expression.
tumor progressionG 4-based modulationwild-type sequenceV loopstructure featuresresonance spectroscopyV-shaped loopnoncanonical G 4V-loop structureKCNN 4 gene encodingG-quadruplex formationguanine-rich minisatellite regionFirst Tandem Repeatgene expressionpotassium channel proteinKCNN 4 expressionG 4sPotassium Channel KCNN 4 Minisatell...G 4 topologycoexisting species