pKID Binds to KIX via an Unstructured Transition State with Nonnative Interactions.
pKID Binds to KIX via an Unstructured Transition State with Nonnative Interactions.
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PKID通过非本地相互作用的非结构化过渡状态与KIX结合。
DOI：
10.1016/j.bpj.2017.10.016
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发表时间：
2017-12-19
影响因子：
3.4
通讯作者：
Clarke J
中科院分区：
文献类型：
--
作者：
Dahal L;Kwan TOC;Shammas SL;Clarke J
了解内在无序蛋白质与其伴侣相互作用的详细机制对于理解它们在信号和转录中的功能至关重要。通过与KIX的相互作用，CREB蛋白无序的pKID区域在cAMP反应基因的转录中起着中心作用，包括那些涉及长期记忆的基因。许多模拟研究都对这些相互作用进行了研究。结合实验结果，这些可以提供有价值的和全面的了解所涉及的机制。在这里，我们通过分析pKID中界面和溶剂暴露残基同时发生突变的动力学效应，从实验上探索了这种相互作用的过渡态。我们发现，在最初的结合过程中，pKID和KIX之间只需要很少的特定相互作用。在过渡态只形成少量的弱相互作用，包括非固有相互作用，大部分折叠发生在初始结合事件之后。这些性质与计算结果一致，也与大多数其他蛋白质体系中固有无序蛋白质偶联折叠和结合的实验研究一致，表明这些可能是共同的特征。
Understanding the detailed mechanism of interaction of intrinsically disordered proteins with their partners is crucial to comprehend their functions in signaling and transcription. Through its interaction with KIX, the disordered pKID region of CREB protein is central in the transcription of cAMP responsive genes, including those involved in long-term memory. Numerous simulation studies have investigated these interactions. Combined with experimental results, these can provide valuable and comprehensive understanding of the mechanisms involved. Here, we probe the transition state of this interaction experimentally through analyzing the kinetic effect of mutating both interface and solvent exposed residues in pKID. We show that very few specific interactions between pKID and KIX are required in the initial binding process. Only a small number of weak interactions are formed at the transition state, including nonnative interactions, and most of the folding occurs after the initial binding event. These properties are consistent with computational results and also the majority of experimental studies of intrinsically disordered protein coupled folding and binding in other protein systems, suggesting that these may be common features.
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影响因子：
4.3
作者：
Ganguly D;Zhang W;Chen J
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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