Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains(384 views) Marasco D, Ruggiero A, Vascotto C, Poletto M, Scognamiglio PL, Tell G, Vitagliano L
Biochemical And Biophysical Research Communications (ISSN: 0006-291x), 2013 Jan 11; 430(2): 523-528.
Keywords: Acute Myeloid Leukemia, Protein Denaturation, Protein Secondary Structure Content, Structure-Stability Relationships, Nucleophosmin, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Chemical Parameters, Chemical Stability, Priority Journal, Protein Analysis, Protein Interaction, Protein Stability, Temperature, Thermostability, Amino Acid Sequence, Heating, Humans, Molecular Chaperones, Molecular Sequence Data, Nuclear Proteins, Protein Multimerization, Protein Structure, Tertiary,
Affiliations: *** IBB - CNR ***
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, I-80134 Napoli, Italy
Department of Biological Sciences, University Federico II of Naples, Via Mezzocannone 16, 80134 Naples, Italy
Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
References: Not available.
Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains
Nucleophosmin (NPM1) is a key factor involved in fundamental biological processes. Mutations involving the NPM1 gene are the most frequent molecular alterations in acute myeloid leukemia. Here we report a biophysical characterization of NPM1 and of its domains in order to gain insights into the role that inter-domain interactions plays in the protein stabilization. Thermal denaturation analyses show that the N-terminal domain is endowed with an exceptional thermal stability, as it does not unfold in the investigated temperature range (20-105 degrees C). This finding is corroborated by chemical denaturation experiments showing that this domain is not significantly affected by the addition of 8 M urea. These results are consistent with the chaperone function of NPM1. In line with literature data, the other folded domain of the NPM1, a 3-helix bundle domain located at the C-terminus, shows a lower stability. Interestingly, the chemical and thermal stability of this latter domain, which embeds natural mutations related to acute myeloid leukemia, is influenced by the presence of other regions of the protein. Small but significant stabilizations of the C-terminal 3-helix bundle are provided by the adjacent unfolded fragment as well as by the rest of the protein. (C) 2012 Elsevier Inc. All rights reserved.
Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(433 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote