Crystal structure of SUMO-modified proliferating cell nuclear antigen.

Crystal structure of SUMO-modified proliferating cell nuclear antigen.
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DOI:
10.1016/j.jmb.2010.12.015
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发表时间:
2011-02-11
影响因子:
5.6
通讯作者:
Washington MT
Washington MT
中科院分区:
生物学2区
文献类型:
--
作者:
Freudenthal BD;Brogie JE;Gakhar L;Kondratick CM;Washington MT

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真核增殖细胞核抗原(PCNA)是一种复制辅助蛋白,在DNA复制、修复和重组中发挥作用。PCNA的各种功能受到翻译后修饰的调节,包括促进跨损伤合成的单泛素化和抑制重组的sumo化。为了理解SUMO修饰如何调节PCNA,我们产生了一种分裂的SUMO修饰的PCNA蛋白,并表明它支持细胞活力并刺激DNA聚合酶δ活性。然后,我们确定其X-射线晶体结构,发现SUMO占据的PCNA环的背面上的位置,这是不同的泛素在泛素修饰的PCNA的结构中所占据的位置。我们认为PCNA的后部已经进化成为一个调节位点,可以很容易地进行修改,而不会破坏PCNA前部正在进行的反应,如正常的DNA复制。此外,这些修饰可能使PCNA发挥工具带的作用,从而蛋白质可以通过PCNA的背面被招募到复制机器中,并保留备用直到需要。
Eukaryotic proliferating cell nuclear antigen (PCNA) is a replication accessory protein that functions in DNA replication, repair, and recombination. The various functions of PCNA are regulated by post-translational modifications including mono-ubiquitylation, which promotes translesion synthesis, and sumoylation, which inhibits recombination. To understand how the SUMO modification regulates PCNA, we generated a split SUMO-modified PCNA protein and showed that it supports cell viability and stimulates DNA polymerase δ activity. We then determined its X-ray crystal structure and found that SUMO occupies a position on the back face of the PCNA ring, which is distinct from the position occupied by ubiquitin in the structure of ubiquitin-modified PCNA. We propose that the back of PCNA has evolved to be a site of regulation that can be easily modified without disrupting ongoing reactions on the front of PCNA, such as normal DNA replication. Moreover, these modifications likely allow PCNA to function as a tool belt, whereby proteins can be recruited to the replication machinery via the back of PCNA and be held in reserve until needed.
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