Intrinsic disorder accelerates dissociation rather than association
Intrinsic disorder accelerates dissociation rather than association
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DOI：
10.1002/prot.25057
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
K. Umezawa;J. Ohnuki;J. Higo;M. Takano
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文献类型：
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作者：
K. Umezawa;J. Ohnuki;J. Higo;M. Takano
固有无序蛋白(IDP)具有独特的物理和生物学特性：当与靶点结合时，它经常折叠，并经常参与信号转导。物理性质似乎与要求IdP和目标之间快速结合和解离的生物性质相一致。虽然快速缔合在飞溅机制的推动下已经得到了很好的研究，但解离动力学却没有得到太多的关注。在这里，我们研究本征无序如何影响解离动力学以及缔合动力学，并注意结合位上的相互作用强度(即“苍蝇诱饵”的质量)。对pKID-KIX系统的粗粒度分子动力学模拟表明，随着赋予模型的无序诱导灵活性的增加，缔合率变大，但随着诱蝇质量的恶化，加速是边缘的，并转变为减速。相反，解离率随着无序的增加而大大增加，这表明内在无序通过解离比关联更有效地用于快速信号切换。蛋白质2016；84：1124-1133。©2016 Wiley期刊，Inc.
The intrinsically disordered protein (IDP) has distinct properties both physically and biologically: it often becomes folded when binding to the target and is frequently involved in signal transduction. The physical property seems to be compatible with the biological property where fast association and dissociation between IDP and the target are required. While fast association has been well studied, fueled by the fly‐casting mechanism, the dissociation kinetics has received less attention. We here study how the intrinsic disorder affects the dissociation kinetics, as well as the association kinetics, paying attention to the interaction strength at the binding site (i.e., the quality of the “fly lure”). Coarse‐grained molecular dynamics simulation of the pKID‐KIX system, a well‐studied IDP system, shows that the association rate becomes larger as the disorder‐inducing flexibility that was imparted to the model is increased, but the acceleration is marginal and turns into deceleration as the quality of the fly lure is worsened. In contrast, the dissociation rate is greatly enhanced as the disorder is increased, indicating that intrinsic disorder serves for rapid signal switching more effectively through dissociation than association. Proteins 2016; 84:1124–1133. © 2016 Wiley Periodicals, Inc.