Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen
Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen
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DOI：
10.1038/nature01691
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发表时间：
2003-05-29
期刊：
影响因子：
64.8
通讯作者：
Chen, XJS
中科院分区：
文献类型：
--
作者：
Li, DW;Zhao, R;Chen, XJS
癌蛋白大肿瘤抗原 (LTag) 由 DNA 肿瘤病毒猿病毒 40 编码。LTag 通过改变肿瘤抑制因子（包括 pRB 和 p53）和其他关键细胞蛋白的功能来转化细胞并诱导动物肿瘤。 LTag 也是一种分子机器，可以扭曲/融化病毒基因组的复制起点并解开双链 DNA。因此，LTag 似乎是真核微染色体维持 (MCM) 复合体的功能同源物。在这里，我们展示了具有 DNA 解旋酶活性的六聚体 LTag 的 X 射线结构。该结构识别了 p53 结合表面并揭示了六聚化的结构基础。六聚体包含一个带正电荷的长通道，具有一个异常大的中央室，可结合单链和双链 DNA。六聚体组织成两层，通过连接α螺旋来扩展/收缩通道，它们可以相对于彼此旋转，产生“虹膜”效应，可用于扭曲或熔化起点并在复制叉处展开DNA。
The oncoprotein large tumour antigen (LTag) is encoded by the DNA tumour virus simian virus 40. LTag transforms cells and induces tumours in animals by altering the functions of tumour suppressors (including pRB and p53) and other key cellular proteins. LTag is also a molecular machine that distorts/melts the replication origin of the viral genome and unwinds duplex DNA. LTag therefore seems to be a functional homologue of the eukaryotic minichromosome maintenance (MCM) complex. Here we present the X-ray structure of a hexameric LTag with DNA helicase activity. The structure identifies the p53-binding surface and reveals the structural basis of hexamerization. The hexamer contains a long, positively charged channel with an unusually large central chamber that binds both single-stranded and double-stranded DNA. The hexamer organizes into two tiers that can potentially rotate relative to each other through connecting alpha-helices to expand/constrict the channel, producing an 'iris' effect that could be used for distorting or melting the origin and unwinding DNA at the replication fork.