Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains
| Autor: | Daniela Marasco, Gianluca Tell, Mattia Poletto, Luigi Vitagliano, Pasqualina Liana Scognamiglio, Carlo Vascotto, Alessia Ruggiero |
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| Přispěvatelé: | Marasco, Daniela, Ruggiero, A, Vascotto, C, Poletto, M, Scognamiglio, Pl, Tell, G, Vitagliano, L. |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
NPM1
Protein Denaturation Structure-stability relationships Molecular Sequence Data Biophysics DNA repair Biochemistry Protein secondary structure content Protein Structure Secondary Heating Protein structure Humans Denaturation (biochemistry) Thermal stability Amino Acid Sequence Molecular Biology Structure–stability relationships Nucleophosmin Acute myeloid leukemia biology Chemistry Protein Stability Myeloid leukemia Nuclear Proteins Cell Biology Protein Structure Tertiary Chaperone (protein) biology.protein Protein denaturation Protein stabilization Protein Multimerization Molecular Chaperones |
| Zdroj: | Biochemical and biophysical research communications 430 (2013): 523–528. doi:10.1016/j.bbrc.2012.12.002 info:cnr-pdr/source/autori:Marasco, Daniela; Ruggiero, Alessia; Vascotto, Carlo; Poletto, Mattia; Scognamiglio, Pasqualina Liana; Tell, Gianluca; Vitagliano, Luigi/titolo:Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains/doi:10.1016%2Fj.bbrc.2012.12.002/rivista:Biochemical and biophysical research communications (Print)/anno:2013/pagina_da:523/pagina_a:528/intervallo_pagine:523–528/volume:430 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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