title: The major G-quadruplex formed in the human platelet-derived growth factor receptor β promoter adopts a novel broken-strand structure in K+ solution.
abstract: Overexpression of platelet-derived growth factor receptor β (PDGFR-β) has been associated with cancers and vascular and fibrotic disorders. PDGFR-β has become an attractive target for the treatment of cancers and fibrotic disorders. DNA G-quadruplexes formed in the GC-rich nuclease hypersensitivity element of the human PDGFR-β gene promoter have been found to inhibit PDGFR-β transcriptional activity. Here we determined the major G-quadruplex formed in the PDGFR-β promoter. Instead of using four continuous runs with three or more guanines, this G-quadruplex adopts a novel folding with a broken G-strand to form a primarily parallel-stranded intramolecular structure with three 1 nucleotide (nt) double-chain-reversal loops and one additional lateral loop. The novel folding of the PDGFR-β promoter G-quadruplex emphasizes the robustness of parallel-stranded structural motifs with a 1 nt loop. Considering recent progress on G-quadruplexes formed in gene-promoter sequences, we suggest the 1 nt looped G(i)NG(j) motif may have been evolutionarily selected to serve as a stable foundation upon which the promoter G-quadruplexes can build. The novel folding of the PDGFR-β promoter G-quadruplex may be attractive for small-molecule drugs that specifically target this secondary structure and modulate PDGFR-β gene expression.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, Arizona 85721, USA.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Chen
authors.forename: Prashansa
authors.initials: P
authors.lastname: Agrawal
authors.forename: Robert V
authors.initials: RV
authors.lastname: Brown
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hatzakis
authors.forename: Laurence
authors.initials: L
authors.lastname: Hurley
authors.forename: Danzhou
authors.initials: D
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006801:Humans; D008969:Molecular Sequence Data; D011188:Potassium / Q000737:chemistry; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012996:Solutions
chemical_list: D012996:Solutions; D020797:Receptor, Platelet-Derived Growth Factor beta; D011188:Potassium