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人细小病毒 B19 非结构蛋白 1 N 端结构域特异性结合到病毒 DNA 复制起点。

The human parvovirus B19 non-structural protein 1 N-terminal domain specifically binds to the origin of replication in the viral DNA.

机构信息

Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

出版信息

Virology. 2014 Jan 20;449:297-303. doi: 10.1016/j.virol.2013.11.031. Epub 2013 Dec 20.

Abstract

The non-structural protein 1 (NS1) of human parvovirus B19 plays a critical role in viral DNA replication. Previous studies identified the origin of replication in the viral DNA, which contains four DNA elements, namely NSBE1 to NSBE4, that are required for optimal viral replication (Guan et al., 2009). Here we have demonstrated in vitro that the NS1 N-terminal domain (NS1N) binds to the origin of replication in a sequence-specific, length-dependent manner that requires NSBE1 and NSBE2, while NSBE3 and NSBE4 are dispensable. Mutagenesis analysis has identified nucleotides in NSBE1 and NSBE2 that are critical for NS1N binding. These results suggest that NS1 binds to the NSBE1-NSBE2 region in the origin of replication, while NSBE3 and NSBE4 may provide binding sites for potential cellular factors. Such a specialized nucleoprotein complex may enable NS1 to nick the terminal resolution site and separate DNA strands during replication.

摘要

人细小病毒 B19 的非结构蛋白 1(NS1)在病毒 DNA 复制中发挥着关键作用。先前的研究确定了病毒 DNA 中的复制起点,其中包含四个 DNA 元件,即 NSBE1 到 NSBE4,它们是最佳病毒复制所必需的(Guan 等人,2009 年)。在这里,我们已经在体外证明 NS1 N 端结构域(NS1N)以序列特异性和长度依赖性的方式与复制起点结合,该结合需要 NSBE1 和 NSBE2,而 NSBE3 和 NSBE4 则是可有可无的。突变分析已经确定了 NSBE1 和 NSBE2 中对 NS1N 结合至关重要的核苷酸。这些结果表明,NS1 结合到复制起点的 NSBE1-NSBE2 区域,而 NSBE3 和 NSBE4 可能为潜在的细胞因子提供结合位点。这种专门的核蛋白复合物可能使 NS1 在复制过程中能够切割末端分辨率位点并分离 DNA 链。

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