Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains

详细信息    查看全文

• 作者：Daniela Marasco^a ; ^b ; ^{daniela.marasco@unina.it} ; Alessia Ruggiero^a ; Carlo Vascotto^c ; Mattia Poletto^c ; Pasqualina Liana Scognamiglio^a ; ^b ; Gianluca Tell^c ; Luigi Vitagliano^a ; ^{luigi.vitagliano@unina.it}
• 关键词：AML ; acute myeloid leukemia ; NPM1 ; Nucleophosmin ; NPM1_fl ; full length Nucleophosmin ; NPM1N-Ter ; residues 1&ndash ; 117 of NPM1 ; NPM1C-Ter108 ; residues 188&ndash ; 294 of NPM1 ; NPM1C-Ter53 ; residues 243&ndash ; 294 of NPM1 ; NPM1C-Ter70 ; residues 226&ndash ; 294 o
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：11 January, 2013
• 年：2013
• 卷：430
• 期：2
• 页码：523-528
• 全文大小：525 K

文摘

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 ¡ãC). 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.