Structural Perspective into the Interaction of an Oncogenesis-Relevant pre-miRNA G-Quadruplex Ligand Carrier with the Protein Nucleolin

Tiago Santos, Micael Silva, Lionel Imbert, Maria P. C. Campello, António Paulo, Samir Amrane, Gilmar F. Salgado, Carla Cruz, Eurico J. Cabrita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The structural determinants of the interaction of the G-quadruplex (G4) motif found in precursor miRNA 149 (rG4) with the acridine orange derivative C8, a G4 ligand stabilizer possessing anticancer activity, and the protein nucleolin (overexpressed in cancer cells) were investigated by Nuclear Magnetic Resonance (NMR) spectroscopy. For the rG4/C8 complex, the results revealed a strong stabilizing interaction between the aromatic core and the iodinated ring of the C8 ligand with the rG4 structure. The NMR study revealed also different interaction patterns between nucleolin and rG4 and nucleolin and rG4/C8 complex. In the absence of the ligand, rG4 establishes interactions with polar residues of the protein while for the rG4/C8 complex, these contacts are mainly established with amino acids that have hydrophobic side chains. However, nucleolin chemical shift perturbation studies in the presence of rG4 or rG4/C8 reveal the same location between domains 1 and 2 of the protein, which suggests that the rG4 and rG4/C8 complex bind in this region. This puzzling structural study opens a new framework to study rG4/ligand/nucleolin complexes that might impact the biogenesis of miRNA 149.

Original languageEnglish
Article numbere202301181
Number of pages9
JournalChemistry - A European Journal
Volume29
Issue number39
DOIs
Publication statusPublished - 11 Jul 2023

Keywords

  • G-quadruplex
  • NMR spectroscopy
  • nucleolin
  • pre-miRNA 149
  • proteins

Fingerprint

Dive into the research topics of 'Structural Perspective into the Interaction of an Oncogenesis-Relevant pre-miRNA G-Quadruplex Ligand Carrier with the Protein Nucleolin'. Together they form a unique fingerprint.

Cite this