Teo Ruijie D, Rousseau Benjamin J G, Smithwick Elizabeth R, Di Felice Rosa, Beratan David N, Migliore Agostino
Department of Chemistry, Duke University, Durham, NC 27708, United States.
Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089, United States.
Chem. 2019 Jan 10;5(1):122-137. doi: 10.1016/j.chempr.2018.09.026. Epub 2018 Oct 25.
Recent experiments suggest that DNA-mediated charge transport might enable signaling between the [4Fe4S] clusters in the C-terminal domains of human DNA primase and polymerase α, as well as the signaling between other replication and repair high-potential [4Fe4S] proteins. Our theoretical study demonstrates that the redox signaling cannot be accomplished exclusively by DNA-mediated charge transport because part of the charge transfer chain has an unfavorable free energy profile. We show that hole or excess electron transfer between a [4Fe4S] cluster and a nucleic acid duplex through a protein medium can occur within microseconds in one direction, while it is kinetically hindered in the opposite direction. We present a set of signaling mechanisms that may occur with the assistance of oxidants or reductants, using the allowed charge transfer processes. These mechanisms would enable the coordinated action of [4Fe4S] proteins on DNA, engaging the [4Fe4S] oxidation state dependence of the protein-DNA binding affinity.
最近的实验表明，DNA介导的电荷传输可能使人类DNA引发酶和聚合酶α C末端结构域中的[4Fe4S]簇之间能够进行信号传递，以及其他复制和修复高电位[4Fe4S]蛋白之间的信号传递。我们的理论研究表明，氧化还原信号不能仅通过DNA介导的电荷传输来完成，因为部分电荷转移链具有不利的自由能分布。我们表明，[4Fe4S]簇与核酸双链体之间通过蛋白质介质的空穴或过量电子转移可以在微秒内在一个方向上发生，而在相反方向上则受到动力学阻碍。我们提出了一组在氧化剂或还原剂的协助下可能发生的信号传导机制，利用允许的电荷转移过程。这些机制将使[4Fe4S]蛋白在DNA上协同作用，涉及蛋白质-DNA结合亲和力对[4Fe4S]氧化态的依赖性。
