Human Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable for YB-1 function. Until now, the roles of the C-terminal extension and phosphorylation in gene transcription and translation are still largely unknown. Here, we solved the structure of human YB-1 CSD with a C-terminal extension sequence (CSDex). The structure reveals that the extension interacts with several residues in the conventional CSD and adopts a rigid structure instead of being disordered. Either deletion of this extension or phosphorylation of S102 destabilizes the protein and results in partial unfolding. Structural characterization of CSDex in complex with a ssDNA heptamer shows that all the seven nucleotides are involved in DNA–protein interactions and the C-terminal extension provides a unique DNA binding site. Our DNA-binding study indicates that CSDex can recognize more DNA sequences than previously thought and the phosphorylation reduces its binding to ssDNA dramatically. Our results suggest that gene transcription and translation can be regulated by changing the affinity of CSDex binding to DNA and RNA through phosphorylation, respectively.

中文翻译：

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DNA结合到人YB-1冷休克结构域的结构基础受磷酸化调节。

人Y盒结合蛋白1（YB-1）是一种多功能蛋白，在许多类型的癌症中均过表达。它通过冷休克域（CSD）特异性识别DNA / RNA，并调节核酸代谢。CSD的C末端延伸和S102的磷酸化对于YB-1功能是必不可少的。到目前为止，C末端延伸和磷酸化在基因转录和翻译中的作用仍是未知之数。在这里，我们解决了具有C末端延伸序列（CSDex）的人YB-1 CSD的结构。该结构表明，延伸部分与常规CSD中的多个残基相互作用，并采用刚性结构而不是无序的。该延伸的缺失或S102的磷酸化都使蛋白质不稳定并导致部分展开。CSDex与ssDNA七聚体的复合结构表征表明，所有七个核苷酸均参与DNA-蛋白质相互作用，并且C端延伸提供了独特的DNA结合位点。我们的DNA结合研究表明，CSDex可以识别比以前认为更多的DNA序列，磷酸化作用极大地降低了其与ssDNA的结合。我们的结果表明，可以通过分别通过磷酸化改变CSDex与DNA和RNA的亲和力来调节基因的转录和翻译。我们的DNA结合研究表明，CSDex可以识别比以前认为更多的DNA序列，并且磷酸化作用极大地降低了其与ssDNA的结合。我们的结果表明，可以通过分别通过磷酸化改变CSDex与DNA和RNA的亲和力来调节基因的转录和翻译。我们的DNA结合研究表明，CSDex可以识别比以前认为更多的DNA序列，磷酸化作用极大地降低了其与ssDNA的结合。我们的结果表明，可以通过分别通过磷酸化改变CSDex与DNA和RNA的亲和力来调节基因的转录和翻译。