Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy.
Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy.
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DOI：
10.1016/j.str.2012.01.011
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发表时间：
2012-03-07
期刊：
影响因子：
5.7
通讯作者：
Li, Huilin
中科院分区：
文献类型：
--
作者：
Sun, Jingchuan;Kawakami, Hironori;Zech, Juergen;Speck, Christian;Stillman, Bruce;Li, Huilin
真核生物起源识别复合体(ORC)在S期启动之前与DNA复制的起始点相互作用并重塑。在此，我们报道了在三磷酸腺苷γS存在下，酿酒酵母ORC、复制起始因子CDC6和双链ARS1源DNA组成的超分子组装的单颗粒低温EM衍生结构。ORC的六个亚基排列为ORc1：orc4：orc5：orc2：orc3，orc6与orc2结合。CDC6结合改变了ORC的构象，特别是重新定位了ORC1N-末端的BAH-结构域。ORC·CDC6在DNA上的3D图谱的分割以及与同源古生菌ORc1/CDC6蛋白晶体结构的对接，表明了一种起源的DNA结合模型，在该模型中，DNA沿着新月形ORC的内表面跟踪。因此，兽人弯曲并包裹着DNA。这个模型与观察到的单个CDC6的结合从两端扩展了原始DNA上的ORC足迹是一致的。
The eukaryotic origin recognition complex (ORC) interacts with and remodels origins of DNA replication prior to initiation in S phase. Here we report single particle cryo-EM-derived structure of the supra-molecular assembly comprising of S. cerevisiae ORC, the replication initiation factor Cdc6 and double strand ARS1 origin DNA in the presence of ATPγS. The six subunits of ORC are arranged as Orc1:Orc4:Orc5:Orc2:Orc3 with Orc6 binding to Orc2. Cdc6 binding changes the conformation of ORC, particularly re-orientating the Orc1 N-terminal BAH-domain. Segmentation of the 3D map of ORC•Cdc6 on DNA and docking with the crystal structure of the homologous archaeal Orc1/Cdc6 protein suggest an origin DNA binding model in which the DNA tracks along the interior surface of the crescent-like ORC. Thus ORC bends and wraps the DNA. This model is consistent with the observation that binding of a single Cdc6 extends the ORC footprint on origin DNA from both ends.
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影响因子：
16
作者：
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通讯作者：
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影响因子：
4.8
作者：
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DOI：
10.1073/pnas.0502946102
发表时间：
2005-06-14
影响因子：
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作者：
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