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Article

Investigation of a Direct Interaction between miR4749 and the Tumor Suppressor p53 by Fluorescence, FRET and Molecular Modeling

Biophysics and Nanoscience Centre, DEB, Università della Tuscia, 01100 Viterbo, Italy
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Biomolecules 2020, 10(2), 346; https://doi.org/10.3390/biom10020346
Received: 8 January 2020 / Revised: 10 February 2020 / Accepted: 20 February 2020 / Published: 22 February 2020
(This article belongs to the Special Issue Recent Advances in p53)
The interactions between the DNA binding domain (DBD) of the tumor suppressor p53 and miR4749, characterized by a high sequence similarity with the DNA Response Element (RE) of p53, was investigated by fluorescence spectroscopy combined with computational modeling and docking. Fluorescence quenching experiments witnessed the formation of a specific complex between DBD and miR4749 with an affinity of about 105 M. Förster Resonance Energy Transfer (FRET) allowed us to measure a distance of 3.9 ± 0.3 nm, between the lone tryptophan of DBD and an acceptor dye suitably bound to miR4749. Such information, combined with a computational modeling approach, allowed us to predict possible structures for the DBD-miR4749 complex. A successive docking refinement, complemented with binding free energy calculations, led us to single out a best model for the DBD-miR4749 complex. We found that the interaction of miR4749 involves the DBD L3 loop and the H1 helix, close to the Zn-finger motif; with this suggesting that miR4749 could directly inhibit the p53 interaction with DNA. These results might inspire new therapeutic strategies finalized to restore the p53 functional activity. View Full-Text
Keywords: miR4749; p53; fluorescence quenching; FRET; computational docking; oncomiR miR4749; p53; fluorescence quenching; FRET; computational docking; oncomiR
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MDPI and ACS Style

Bizzarri, A.R.; Cannistraro, S. Investigation of a Direct Interaction between miR4749 and the Tumor Suppressor p53 by Fluorescence, FRET and Molecular Modeling. Biomolecules 2020, 10, 346. https://doi.org/10.3390/biom10020346

AMA Style

Bizzarri AR, Cannistraro S. Investigation of a Direct Interaction between miR4749 and the Tumor Suppressor p53 by Fluorescence, FRET and Molecular Modeling. Biomolecules. 2020; 10(2):346. https://doi.org/10.3390/biom10020346

Chicago/Turabian Style

Bizzarri, Anna R., and Salvatore Cannistraro. 2020. "Investigation of a Direct Interaction between miR4749 and the Tumor Suppressor p53 by Fluorescence, FRET and Molecular Modeling" Biomolecules 10, no. 2: 346. https://doi.org/10.3390/biom10020346

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