2LLH

NMR structure of Npm1_c70

2LLH の概要

• エントリーDOI: 10.2210/pdb2llh/pdb
• 関連するPDBエントリー: 2VXD
• NMR情報: BMRB: 18048
• 分子名称: Nucleophosmin (1 entity in total)
• 機能のキーワード: nucleolar, chaperone, oncoprotein, dna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleolus: P06748
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8514.80

構造登録者

Banci, L.,Bertini, I.,Brunori, M.,Di Matteo, A.,Federici, L.,Gallo, A.,Lo Sterzo, C.,Mori, M. (登録日: 2011-11-09, 公開日: 2012-06-27, 最終更新日: 2024-05-15)

主引用文献

Gallo, A.,Lo Sterzo, C.,Mori, M.,Di Matteo, A.,Bertini, I.,Banci, L.,Brunori, M.,Federici, L.
Structure of Nucleophosmin DNA-binding Domain and Analysis of Its Complex with a G-quadruplex Sequence from the c-MYC Promoter.
J.Biol.Chem., 287:26539-26548, 2012

PubMed Abstract: Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, mainly localized at nucleoli, that plays a key role in several cellular functions, including ribosome maturation and export, centrosome duplication, and response to stress stimuli. More than 50 mutations at the terminal exon of the NPM1 gene have been identified so far in acute myeloid leukemia; the mutated proteins are aberrantly and stably localized in the cytoplasm due to high destabilization of the NPM1 C-terminal domain and the appearance of a new nuclear export signal. We have shown previously that the 70-residue NPM1 C-terminal domain (NPM1-C70) is able to bind with high affinity a specific region at the c-MYC gene promoter characterized by parallel G-quadruplex structure. Here we present the solution structure of the NPM1-C70 domain and NMR analysis of its interaction with a c-MYC-derived G-quadruplex. These data were used to calculate an experimentally restrained molecular docking model for the complex. The NPM1-C70 terminal three-helix bundle binds the G-quadruplex DNA at the interface between helices H1 and H2 through electrostatic interactions with the G-quadruplex phosphate backbone. Furthermore, we show that the 17-residue lysine-rich sequence at the N terminus of the three-helix bundle is disordered and, although necessary, does not participate directly in the contact surface in the complex.

PubMed: 22707729
DOI: 10.1074/jbc.M112.371013

実験手法

SOLUTION NMR