Importance of electrostatic interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B.
Importance of electrostatic interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B.
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静电相互作用在本质无序组蛋白伴侣 Chz1 和组蛋白 H2A.Z-H2B 关联中的重要性
DOI：
10.1371/journal.pcbi.1002608
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发表时间：
2012
影响因子：
4.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Chu X;Wang Y;Gan L;Bai Y;Han W;Wang E;Wang J
组蛋白伴侣促进核小体的组装和拆卸。了解组蛋白伴侣如何与组蛋白结合和分离的过程有助于阐明它们在染色体代谢中的作用。一些组蛋白伴侣是内在无序蛋白（IDP）。最近的研究表明，IDPs的生物分子的识别是通过灵活性和动力学实现的，挑战了百年的结构-功能范式。基于Chz 1和H2 A. Z-H2 B的高电荷特性，采用Debye-Hückel模型描述Chz 1和H2 A. Z-H2 B之间的静电相互作用，建立了一个基于结构的粗粒模型，研究了Chz 1和H2 A. Z-H2 B之间的结合.我们发现，主要的结构变化的Chz 1只发生后，限速静电占主导地位的过渡态和Chz 1通过两个平行的途径进行折叠耦合结合。有趣的是，虽然静电相互作用稳定结合的复合物，并促进在第一阶段的识别，复合物的形成速率并不总是加速，由于在低盐浓度下的非天然静电相互作用的构象的缓慢逃逸。我们的研究提供了一个离子强度控制的结合/折叠机制，导致了“局部崩溃或捕获”和“飞投”一起的合作机制和静电相互作用在IDP的结合中的作用的新的理解。
Histone chaperones facilitate assembly and disassembly of nucleosomes. Understanding the process of how histone chaperones associate and dissociate from the histones can help clarify their roles in chromosome metabolism. Some histone chaperones are intrinsically disordered proteins (IDPs). Recent studies of IDPs revealed that the recognition of the biomolecules is realized by the flexibility and dynamics, challenging the century-old structure-function paradigm. Here we investigate the binding between intrinsically disordered chaperone Chz1 and histone variant H2A.Z-H2B by developing a structure-based coarse-grained model, in which Debye-Hückel model is implemented for describing electrostatic interactions due to highly charged characteristic of Chz1 and H2A.Z-H2B. We find that major structural changes of Chz1 only occur after the rate-limiting electrostatic dominant transition state and Chz1 undergoes folding coupled binding through two parallel pathways. Interestingly, although the electrostatic interactions stabilize bound complex and facilitate the recognition at first stage, the rate for formation of the complex is not always accelerated due to slow escape of conformations with non-native electrostatic interactions at low salt concentrations. Our studies provide an ionic-strength-controlled binding/folding mechanism, leading to a cooperative mechanism of “local collapse or trapping” and “fly-casting” together and a new understanding of the roles of electrostatic interactions in IDPs' binding.
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通过弛豫分散核磁共振波谱研究组蛋白伴侣 Chz1 和变体组蛋白 H2A.Z-H2B 的结合动力学。
影响因子：
5.6
作者：
Hansen, D. Flemming;Zhou, Zheng;Fen, Haniqiao;Jenkins, Lisa M. Miller;Bai, Yawen;Kay, Lewis E.
通讯作者：
Kay, Lewis E.
影响因子：
64.8
作者：
LASKEY, RA;HONDA, BM;FINCH, JT
通讯作者：
FINCH, JT
影响因子：
13.8
作者：
Das, Chandrima;Tyler, Jessica K.;Churchill, Mair E. A.
通讯作者：
Churchill, Mair E. A.
影响因子：
6.8
作者：
Dunker, A. Keith;Silman, Israel;Sussman, Joel L.
通讯作者：
Sussman, Joel L.
影响因子：
5.6
作者：
Clementi, C;Nymeyer, H;Onuchic, JN
通讯作者：
Onuchic, JN