Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.
Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.
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DOI：
10.1038/s41467-018-05406-y
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发表时间：
2018-08-06
影响因子：
16.6
通讯作者：
Chan NL
中科院分区：
文献类型：
--
作者：
Chen SF;Huang NL;Lin JH;Wu CC;Wang YR;Yu YJ;Gilson MK;Chan NL
IIA型拓扑异构酶（Top2）通过在一个DNA双链体中引入瞬时和蛋白质连接的双链断裂来操纵DNA交换的手性，称为DNA门，其打开允许另一个DNA片段被运输通过以改变DNA拓扑结构。尽管这种门打开事件对Top2功能至关重要，但在所有报道的Top2-DNA复合物结构中的DNA门都处于关闭状态。在这里，我们提出了一个人的Top2 DNA门的晶体结构在一个开放的构象，这不仅揭示了其DNA传导路径的结构特征，但也揭示了意想不到的，但功能上显着的构象变化与门开放。这种结构进一步暗示了Top2对左手DNA辫子的偏好，并允许构建代表另一个DNA双链体初始进入DNA门的模型。导向分子动力学计算表明，Top2催化的DNA通道可以通过DNA门的摇杆开关型运动来实现。II型DNA拓扑异构酶（Top2）指导一个DNA双链体通过另一个，这对解决DNA缠结很重要。在这里，作者结合联合收割机X射线晶体学和MD模拟，并提出了人类Top2 DNA门的结构在一个开放的构象，并讨论机制的影响。
Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2’s preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate. Type II DNA topoisomerases (Top2s) direct the passage of one DNA duplex through another, which is important for resolving DNA entanglements. Here the authors combine X-ray crystallography and MD simulations and present the structure of the human Top2 DNA-gate in an open conformation and discuss mechanistic implications.
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影响因子：
5
作者：
Collin, Frederic;Karkare, Shantanu;Maxwell, Anthony
通讯作者：
Maxwell, Anthony
影响因子：
10.5
作者：
Crisona, NJ;Strick, TR;Cozzarelli, NR
通讯作者：
Cozzarelli, NR
影响因子：
64.8
作者：
Dong, Ken C.;Berger, James M.
通讯作者：
Berger, James M.
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH