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 contribution
posted on 2021-04-12, 17:08 authored by Yoanes
Maria Vianney, Klaus WeiszThe 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.
History
Usage metrics
Categories
Keywords
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