A Cytotoxic Ribonuclease Variant with a Discontinuous Nuclear Localization Signal Constituted by Basic Residues Scattered Over Three Areas of the Molecule
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- 作者：M. Rodrí ; guez ; A. Benito ; P. Tubert ; J. Castro ; M. Ribó ; B. Beaumelle and M. Vilanova
- 关键词：human pancreatic ribonuclease ; NLS ; importin α ; molecular recognition ; protein– ; protein interactions
- 刊名：Journal of Molecular Biology
- 出版年：2006
- 出版时间：14 July 2006
- 年：2006
- 卷：360
- 期：3
- 页码：548-557
- 全文大小：739 K
文摘
Nuclear import of proteins is determined by specific signals that allow them to bind to receptors that mediate their energy-dependent transport through the nuclear pore. These signals are termed nuclear localization signals and do not constitute a specific consensus sequence. Among them, the most characterized correspond to monopartite and bipartite nuclear localization signals, which interact with the importin α/β heterodimer. We previously described a cytotoxic variant of human pancreatic-ribonuclease that is actively transported into the nucleus. Here, we show that this protein interacts with importin α through different basic residues, including Lys1 and the arginine clusters 31–33 and 89–91. Although these residues are scattered along the sequence, they are close in the three-dimensional structure of the protein and their topological disposition strongly resembles that of a classical bipartite nuclear localization signal.