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8S1W

Structure of a quadruplex-duplex hybrid with a (-pd+l) loop progression

Summary for 8S1W
Entry DOI10.2210/pdb8s1w/pdb
NMR InformationBMRB: 34900
DescriptorDNA (33-MER) (1 entity in total)
Functional Keywords(3+1) hybrid, dna, diagonal loop, g-quadruplex, lateral loop, propeller loop, quadruplex-duplex hybrid
Biological sourcesynthetic construct
Total number of polymer chains1
Total formula weight10467.54
Authors
Vianney, Y.M.,Jana, J.,Weisz, K. (deposition date: 2024-02-16, release date: 2024-03-27, Last modification date: 2024-06-05)
Primary citationVianney, Y.M.,Jana, J.,Weisz, K.
A pH-Responsive Topological Switch Based on a DNA Quadruplex-Duplex Hybrid.
Chemistry, 30:e202400722-e202400722, 2024
Cited by
PubMed Abstract: A guanine-rich oligonucleotide based on a human telomeric sequence but with the first three-nucleotide intervening stretch replaced by a putative 15-nucleotide hairpin-forming sequence shows a pH-dependent folding into different quadruplex-duplex hybrids in a potassium containing buffer. At slightly acidic pH, the quadruplex domain adopts a chair-type conformation. Upon increasing the pH, a transition with a midpoint close to neutral pH to a major and minor (3+1) hybrid topology with either a coaxially stacked or orthogonally oriented duplex stem-loop occurs. NMR-derived high-resolution structures reveal that an adenine protonation is prerequisite for the formation of a non-canonical base quartet, capping the outer G-tetrad at the quadruplex-duplex interface and stabilizing the antiparallel chair conformation in an acidic environment. Being directly associated with interactions at the quadruplex-duplex interface, this unique pH-dependent topological transition is fully reversible. Coupled with a conformation-sensitive optical readout demonstrated as a proof of concept using the fluorescent dye thiazole orange, the present quadruplex-duplex hybrid architecture represents a potentially valuable pH-sensing system responsive in a physiological pH range of 7±1.
PubMed: 38497675
DOI: 10.1002/chem.202400722
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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