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

17/05/2023

<jats:title>Abstract</jats:title><jats:p>The structural determinants of the interaction of the G‐quadruplex (G4) motif found in precursor miRNA 149 (rG4) with the acridine orange derivative C<jats:sub>8</jats:sub>, 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/C<jats:sub>8</jats:sub> complex, the results revealed a strong stabilizing interaction between the aromatic core and the iodinated ring of the C<jats:sub>8</jats:sub> ligand with the rG4 structure. The NMR study revealed also different interaction patterns between nucleolin and rG4 and nucleolin and rG4/C<jats:sub>8</jats:sub> complex. In the absence of the ligand, rG4 establishes interactions with polar residues of the protein while for the rG4/C<jats:sub>8</jats:sub> 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/C<jats:sub>8</jats:sub> reveal the same location between domains 1 and 2 of the protein, which suggests that the rG4 and rG4/C<jats:sub>8</jats:sub> 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.</jats:p>

Autores da comunidade :

• 

  M

  Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros

  ist25375

  Afiliações e fontes

  IST > DECN

  Departamento de Engenharia e Ciências Nucleares

  IST > C2TN

  Centro de Ciências e Tecnologias Nucleares

  De: cienciavitae

  ID: 3288935

AO - Versão original do autor

Wiley

Chemistry – A European Journal

29

39

0947-6539

10.1002/chem.202301181

chemical-sciences - Química

eng - Inglês

https://scholar.tecnico.ulisboa.pt/records/9hueMKKlV7IYmO_Qd9cCSOPN12hOd98mh000