通过CRM1识别富含白的核出口信号的结构基础
Xiuhua Dong1, Anindita Biswas, Katherine E Süel
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.
Nature
|April 3, 2009
概括
该研究揭示了CRM1 (exportin 1) 如何与核出口蛋白结合,详细介绍了与snurportin 1的双重相互作用. 这种结构性洞察力解释了CRM1.
科学领域:
- 结构生物学 结构生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- CRM1 (出口因1) 对于通过富含白的核出口信号 (LR-NES) 来核出口蛋白质至关重要.
- 了解CRM1-基板相互作用是破译核运输法规的关键.
研究的目的:
- 为了阐明CRM1识别和绑定其货物的结构基础,snurportin 1 (SNUPN).
- 描述涉及CRM1中介核出口的分子相互作用.
主要方法:
- 在2.9 Å分辨率的X射线晶体学以确定CRM1与SNUPN结合的结构.
- 蛋白质-蛋白质接口和相互作用模式的分析.
主要成果:
- 2.9 Å 结构显示,SNUPN 通过双边相互作用与 CRM1 结合:一个 N-终端的 LR-NES 和它的核酸结合域.
- 该LR-NES形成一个阿尔法螺旋式延伸结构,适合CRM1.1上的疏水槽.
- 第二个相互作用涉及SNUPN的基本表面与CRM1上的酸性补丁结合,与LR-NES位置相邻.
结论:
- 多方识别,涉及多个弱结合点,可能是CRM1基质的常见机制,增强结合亲和力.
- 这种具有约束力的战略提供了广泛的基质特异性,并促进了核运输途径的快速演变.
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