Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport.
Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport.
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DOI：
10.1093/nar/gkt749
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发表时间：
2013-11
影响因子：
14.9
通讯作者：
Sanderson MR
中科院分区：
文献类型：
--
作者：
Laponogov I;Veselkov DA;Crevel IM;Pan XS;Fisher LM;Sanderson MR
II型拓扑异构酶调节DNA超螺旋和染色体分离。它们充当ATP操作的夹子，捕获DNA双链体，并通过ATP酶-、G-DNA-和C-门的顺序打开和关闭使其通过第二DNA片段中的瞬时DNA断裂。在这里，我们提出了第一个“开放钳”结构的3门拓扑异构酶II-DNA复合物，精液复杂的DNA识别和捕获。解析了肺炎链球菌拓扑异构酶IV的（全长ParE-ParC 55）2二聚体的高分辨率结构，所述二聚体结合到两个DNA分子：B-A-B形式双螺旋构象的闭合DNA门和在邻近催化重要的β-风车DNA结合结构域的新位点处与闭合C门螺旋相关的第二B形式双链体。蛋白N门以“臂宽打开”状态存在，其中未二聚化的N-末端帕雷ATP酶结构域通过柔性接头连接至TOPRIM结构域并折叠回，从而允许门和运输的DNA片段以及裂解稳定的抗菌药物容易进入。该结构显示了所有三个门在3.7 nm处的分子构象，这是迄今为止完整复合物达到的最高分辨率，并阐明了II型拓扑异构酶捕获和转运DNA的机制。
Type II topoisomerases regulate DNA supercoiling and chromosome segregation. They act as ATP-operated clamps that capture a DNA duplex and pass it through a transient DNA break in a second DNA segment via the sequential opening and closure of ATPase-, G-DNA- and C-gates. Here, we present the first ‘open clamp’ structures of a 3-gate topoisomerase II-DNA complex, the seminal complex engaged in DNA recognition and capture. A high-resolution structure was solved for a (full-length ParE-ParC55)2 dimer of Streptococcus pneumoniae topoisomerase IV bound to two DNA molecules: a closed DNA gate in a B-A-B form double-helical conformation and a second B-form duplex associated with closed C-gate helices at a novel site neighbouring the catalytically important β-pinwheel DNA-binding domain. The protein N gate is present in an ‘arms-wide-open’ state with the undimerized N-terminal ParE ATPase domains connected to TOPRIM domains via a flexible joint and folded back allowing ready access both for gate and transported DNA segments and cleavage-stabilizing antibacterial drugs. The structure shows the molecular conformations of all three gates at 3.7 Å, the highest resolution achieved for the full complex to date, and illuminates the mechanism of DNA capture and transport by a type II topoisomerase.
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肺炎链球菌的断裂 - 重新结构域IV：革兰氏阳性喹诺酮靶标的晶体结构。
影响因子：
3.7
作者：
Laponogov I;Veselkov DA;Sohi MK;Pan XS;Achari A;Yang C;Ferrara JD;Fisher LM;Sanderson MR
通讯作者：
Sanderson MR
影响因子：
3.7
作者：
Laponogov I;Pan XS;Veselkov DA;McAuley KE;Fisher LM;Sanderson MR
通讯作者：
Sanderson MR
影响因子：
4.9
作者：
Bellon, S;Parsons, JD;Gross, CH
通讯作者：
Gross, CH
影响因子：
5
作者：
Collin, Frederic;Karkare, Shantanu;Maxwell, Anthony
通讯作者：
Maxwell, Anthony
影响因子：
64.8
作者：
Dong, Ken C.;Berger, James M.
通讯作者：
Berger, James M.