Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase.
Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase.
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作者：
Chu X;Suo Z;Wang J
多结构域蛋白质折叠的方式几十年来一直是一个令人困惑的问题。到目前为止，结构域相互作用参与多结构域蛋白质折叠的机制和功能还不清楚。在这里，我们开发了基于结构的模型来研究多结构域Y家族DNA聚合酶IV（DPO 4）的折叠和DNA结合过程。我们发现有序域折叠，回溯折叠，合作折叠，调制域间的相互作用之间的折叠机制的转变。这些导致“U形”DPO 4折叠动力学。我们表征了结构域间的灵活性对DPO 4-DNA（UN）结合的促进作用，这可能有助于DPO 4绕过DNA损伤的能力，这是Y家族聚合酶的已知生物学作用。我们认为，DPO 4的天然拓扑结构导致快速，稳定的折叠和紧密的功能性DNA结合之间的权衡。我们的方法提供了一种有效的方法来定量相关的蛋白质相互作用的构象动力学在多域水平的作用。
The way in which multidomain proteins fold has been a puzzling question for decades. Until now, the mechanisms and functions of domain interactions involved in multidomain protein folding have been obscure. Here, we develop structure-based models to investigate the folding and DNA-binding processes of the multidomain Y-family DNA polymerase IV (DPO4). We uncover shifts in the folding mechanism among ordered domain-wise folding, backtracking folding, and cooperative folding, modulated by interdomain interactions. These lead to ‘U-shaped’ DPO4 folding kinetics. We characterize the effects of interdomain flexibility on the promotion of DPO4–DNA (un)binding, which probably contributes to the ability of DPO4 to bypass DNA lesions, which is a known biological role of Y-family polymerases. We suggest that the native topology of DPO4 leads to a trade-off between fast, stable folding and tight functional DNA binding. Our approach provides an effective way to quantitatively correlate the roles of protein interactions in conformational dynamics at the multidomain level.
影响因子：
2.9
作者：
Maxwell BA;Xu C;Suo Z
通讯作者：
Suo Z