Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β.
Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β.
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DOI：
10.3389/fmolb.2021.716477
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发表时间：
2021
影响因子：
5
通讯作者：
Cho JH
中科院分区：
文献类型：
--
作者：
Dubrow A;Kim I;Topo E;Cho JH
生物分子识别通常涉及构象变化作为结合的先决条件（即，构象选择）或与结合同时进行（即，诱导拟合）。结构和动力学方法的最新进展使蛋白质运动的原子分辨率的详细表征。然而，为了充分了解构象动力学在分子识别中的作用，需要对结合过渡态进行研究。在这里，我们研究了1918年大流行性甲型流感病毒的非结构蛋白1（NS1）和PI3K的人p85β亚基之间的结合过渡态。1918 NS1通过构象选择与p85β结合。利用线性自由能关系和自由能值分析，给出了1918 NS 1：p85β相互作用的过渡态和束缚态的自由能映射.我们发现1918 NS1和p85β的结合过渡态在结构上类似于结合态，具有明确的结合方向和疏水相互作用。我们的发现提供了一个详细的视图如何蛋白质运动有助于分子间相互作用的发展沿着结合反应坐标。
Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic resolution. However, to fully understand the role of the conformational dynamics in molecular recognition, studies on the binding transition state are needed. Here, we investigate the binding transition state between nonstructural protein 1 (NS1) of the pandemic 1918 influenza A virus and the human p85β subunit of PI3K. 1918 NS1 binds to p85β via conformational selection. We present the free-energy mapping of the transition and bound states of the 1918 NS1:p85β interaction using linear free energy relationship and ϕ-value analyses. We find that the binding transition state of 1918 NS1 and p85β is structurally similar to the bound state with well-defined binding orientation and hydrophobic interactions. Our finding provides a detailed view of how protein motion contributes to the development of intermolecular interactions along the binding reaction coordinate.
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DOI：
10.1073/pnas.031575198
发表时间：
2001-02-27
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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影响因子：
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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：
15
作者：
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通讯作者：
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