Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex
Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex
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DOI：
10.1038/nature02585
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发表时间：
2004-06-17
期刊：
影响因子：
64.8
通讯作者：
Kuriyan, J
中科院分区：
文献类型：
--
作者：
Bowman, GD;O'Donnell, M;Kuriyan, J
滑动夹是环绕DNA并赋予DNA聚合酶高加工性的环状蛋白质。在这里，我们报道了酿酒酵母五蛋白钳夹复合体(复制因子-C，RFC)的晶体结构，该复合体与滑动钳(增殖细胞核抗原)结合。RFC与三磷酸腺苷类似物S的紧密界面配位导致钳制加载器的ATPase结构域在增殖细胞核抗原环上方螺旋排列。将DNA启动模型放置在增殖细胞核抗原的中心孔内，揭示了RFC螺旋和DNA双螺旋的凹槽之间惊人的对应关系。在这个模型中，钳位加载器复合体以螺帽状的排列锁定到启动的DNA上，为RFC：PCNA复合体与引物-模板连接导致ATP水解和DNA上滑动钳释放的过程提供了一个简单的解释。
Sliding clamps are ring-shaped proteins that encircle DNA and confer high processivity on DNA polymerases. Here we report the crystal structure of the five-protein clamp loader complex ( replication factor-C, RFC) of the yeast Saccharomyces cerevisiae, bound to the sliding clamp ( proliferating cell nuclear antigen, PCNA). Tight interfacial coordination of the ATP analogue ATP-gamma S by RFC results in a spiral arrangement of the ATPase domains of the clamp loader above the PCNA ring. Placement of a model for primed DNA within the central hole of PCNA reveals a striking correspondence between the RFC spiral and the grooves of the DNA double helix. This model, in which the clamp loader complex locks onto primed DNA in a screw-cap-like arrangement, provides a simple explanation for the process by which the engagement of primer-template junctions by the RFC: PCNA complex results in ATP hydrolysis and release of the sliding clamp on DNA.