Protein metamorphosis: the two-state behavior of Mad2.

Protein metamorphosis: the two-state behavior of Mad2.
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DOI:
10.1016/j.str.2008.10.002
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发表时间:
2008-11-12
期刊:
影响因子:
5.7
通讯作者:
Yu, Hongtao
Yu, Hongtao
中科院分区:
生物学2区
文献类型:
--
作者:
Luo, Xuelian;Yu, Hongtao

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给定的蛋白质通常只有一个天然三级折叠,这是具有最低吉布斯自由能的构象。Mad 2是一种参与纺锤体检查点的蛋白质,它具有两种具有相似吉布斯自由能的天然折叠状态。Mad 2通过与其靶Cdc 20结合,抑制多亚基泛素连接酶,后期促进复合物或细胞周期体(APC/C),并延迟后期的开始,直到所有姐妹染色单体实现双极附着到有丝分裂纺锤体。在没有配体结合或共价修饰的情况下,Mad 2在生理条件下平衡时采用两种拓扑和功能不同的天然折叠。两种Mad 2状态之间的转换受多种机制调节,并且对纺锤体检查点的激活和失活至关重要。本文综述了最近关于Mad 2双态行为的结构和生化研究,并讨论了蛋白质结构可塑性的普遍性和影响。
A given protein generally has only one native tertiary fold, which is the conformation with the lowest Gibbs free energy. Mad2, a protein involved in the spindle checkpoint, however, has two natively folded states with similar Gibbs free energies. Through binding to its target Cdc20, Mad2 inhibits the multisubunit ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C), and delays the onset of anaphase until all sister chromatids achieve bipolar attachment to the mitotic spindle. Without ligand binding or covalent modifications, Mad2 adopts two topologically and functionally distinct native folds in equilibrium under physiological conditions. The transition between the two Mad2 states is regulated by multiple mechanisms and is central to the activation and inactivation of the spindle checkpoint. This review summarizes recent structural and biochemical studies on the two-state behavior of Mad2 and discusses the generality and implications of structural malleability of proteins.
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