9P9Y

Solution structure of the major PDGFRB promoter G-quadruplex with a broken-strand G21 fill-in

Summary for 9P9Y

• Entry DOI: 10.2210/pdb9p9y/pdb
• NMR Information: BMRB: 31253
• Descriptor: DNA (5'-D(*AP*AP*GP*GP*GP*AP*GP*GP*GP*CP*GP*GP*CP*GP*GP*GP*GP*CP*AP*GP*G)-3') (1 entity in total)
• Functional Keywords: g-quadruplex dna, pdgfrb, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 6684.30

Authors

Han, Y.,Dickerhoff, J.,Yang, D. (deposition date: 2025-06-25, release date: 2026-08-26, Last modification date: 2026-09-16)

Primary citation

Han, Y.,Dickerhoff, J.,Yang, D.
Structures and dynamics of the major G-quadruplex in the human PDGFR-beta gene promoter: insights into vacancy G-quadruplex formation.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: Overexpression of PDGFR-β (platelet-derived growth factor receptor beta) kinase contributes to diverse human diseases, including cancers, cardiovascular disorders, and fibrosis. G-quadruplexes (G4s) formed in the PDGFR-β promoter act as transcriptional repressors and represent attractive therapeutic targets. We previously reported that the major G4-forming region of the PDGFR-β promoter adopts a unique broken-strand G4, whereas truncation of this sequence generates a vacancy G4 (vG4) that can be filled-in by external guanine analogs or metabolites and further stabilized by small molecules, suggesting a potential regulatory mechanism and opportunity for selective drug targeting. However, the relationship between broken-strand G4s and vG4s remains unclear. Here, we demonstrate that the PDGFR-β promoter sequence forms a dynamic equilibrium between two broken-strand G4 conformations that interconvert on the millisecond timescale, with vG4 serving as an intermediate. We determined the high-resolution NMR structures of these interconverting G4s, which share a conserved vG4 core but differ in their intramolecular guanine "fill-in." Both conformations feature a stabilizing G-G capping base pair unique to the PDGFR-β promoter. These findings elucidate the structural details of broken-strand PDGFR-β promoter G4s and the mechanism of vG4 formation, providing critical insights for selective drug targeting and establishing a framework for rational design of small molecules to modulate PDGFR-β transcription.

PubMed: 42695283
DOI: 10.1093/nar/gkag843

Experimental method

SOLUTION NMR