MIND综合体的结构定义了酵母动态组装的监管重点
Yoana N Dimitrova1, Simon Jenni1, Roberto Valverde1
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Cell
|November 25, 2016
概括
MIND复合体将中间体连接到微管. 它的结构揭示了Dsn1酸化如何通过控制与Mif2,COMA和Ndc80复合体的相互作用来调节动态细胞组合.
科学领域:
- 细胞生物学
- 结构生物学
- 分子生物学
背景情况:
- 在细胞分裂过程中,Kinetochores是关键的蛋白质结构,它连接着中心DNA与螺旋小管.
- MIND复合体 (Mtw1, Nnf1, Nsl1, Dsn1) 是动态的一个关键组成部分,类似于甲状动物的 Mis12复合体.
- MIND与微管结合的 Ndc80 复合体连接了中心和近端元素 (Mif2,COMA).
研究的目的:
- 要确定Kluyveromyces lactis MIND复合物的晶体结构.
- 阐明MIND在运动细胞组合和微管附着中的分子机制.
- 了解MIND如何集成用于动态动核形成的调节信号.
主要方法:
- 进行X射线晶体学,以获得Kluyveromyces lactis MIND复合物的高分辨率结构.
- 分析蛋白与蛋白相互作用和调节机制的生物化学测试.
- 基于结构的保存域和交互接口的分析.
主要成果:
- 这种MIND复合体采用了长长的,不对称的Y形结构,有两个球形头和一个卷轴轴.
- 一个N端Dsn1扩展作为一个自抑制域,阻断Mif2/COMA结合.
- 通过Ipl1/Aurora B激酶对Dsn1的酸化缓解了自身抑制,促进了激素组合.
- 一个C端Dsn1扩展作为Ndc80复合体的对接点.
结论:
- 该MIND复杂结构透露了一种通过自抑制和调节来调节动态细胞组合的复杂机制.
- Dsn1在整合中导体和微管结合元件方面发挥着核心作用.
- 这项研究提供了原子层面的洞察力,
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