title: G-quadruplex DNA recognition by nucleophosmin: new insights from protein dissection.
abstract: BACKGROUND
  Nucleophosmin (NPM1, B23) is a multifunctional protein that is involved in a variety of fundamental biological processes. NPM1/B23 deregulation is implicated in the pathogenesis of several human malignancies. This protein exerts its functions through the interaction with a multiplicity of biological partners. Very recently it is has been shown that NPM1/B23 specifically recognizes DNA G-quadruplexes through its C-terminal region.
  
  
  METHODS
  Through a rational dissection approach of protein here we show that the intrinsically unfolded regions of NPM1/B23 significantly contribute to the binding of c-MYC G-quadruplex motif. Interestingly, the analysis of the ability of distinct NPM1/B23 fragments to bind this quadruplex led to the identifications of distinct NPM1/B23-based peptides that individually present a high affinity for this motif.
  
  
  RESULTS
  These results suggest that the tight binding of NPM1/B23 to the G-quadruplex is achieved through the cooperation of both folded and unfolded regions that are individually able to bind it. The dissection of NPM1/B23 also unveils that its H1 helix is intrinsically endowed with an unusual thermal stability.
  
  
  CONCLUSIONS
  These findings have implications for the unfolding mechanism of NPM1/B23, for the G-quadruplex affinity of the different NPM1/B23 isoforms and for the design of peptide-based molecules able to interact with this DNA motif.
  This study sheds new light in the molecular mechanism of the complex NPM1/G-quadruplex involved in acute myeloid leukemia (AML) disease.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy; Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT), 80125 Naples, Italy.
authors.forename: Pasqualina Liana
authors.initials: PL
authors.lastname: Scognamiglio
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy; Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT), 80125 Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Di Natale
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, 80134 Naples, Italy; CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Leone
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Poletto
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, 80134 Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy; CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy. Electronic address: daniela.marasco@unina.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
mesh_terms: D000595:Amino Acid Sequence; D054856:G-Quadruplexes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D000090243:Nucleophosmin; D017510:Protein Folding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: C489427:MYC protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D000090243:Nucleophosmin
keywords: Disordered protein region; Helical stability; Surface Plasmon Resonance