Braunstein Jutta, Brutsaert Siska, Olson Rich, Schindler Christian
Department of Microbiology, Columbia University, New York, New York 10032, USA.
J Biol Chem. 2003 Sep 5;278(36):34133-40. doi: 10.1074/jbc.M304531200. Epub 2003 Jun 28.
Upon activation by tyrosine kinases, members of the STAT family of transcription factors form stable dimers that are able to rapidly translocate to the nucleus and bind DNA. Although crystal structures of activated, near full-length, Stat1 and Stat3 illustrate how STATs bind to DNA, they provide little insight into the dynamic regulation of STAT activity. To explore the unique structural changes Stat1 and Stat3 undergo when they become activated, full-length inactive recombinant proteins were prepared. To our surprise, even though these proteins are unable to bind DNA, our studies demonstrate that they exist as stable homodimers. Similarly, the Stat1 and Stat3 found in the cytoplasm of unstimulated cells also exhibit a dimeric structure. These observations indicate that Stat1 and Stat3 exist as stable homodimers prior to activation.
在被酪氨酸激酶激活后，转录因子STAT家族的成员会形成稳定的二聚体，这些二聚体能够迅速转移到细胞核并结合DNA。尽管活化的、接近全长的Stat1和Stat3的晶体结构说明了STAT如何与DNA结合，但它们对STAT活性的动态调节提供的见解很少。为了探索Stat1和Stat3激活时所经历的独特结构变化，制备了全长无活性重组蛋白。令我们惊讶的是，尽管这些蛋白无法结合DNA，但我们的研究表明它们以稳定的同源二聚体形式存在。同样，在未受刺激细胞的细胞质中发现的Stat1和Stat3也呈现二聚体结构。这些观察结果表明，Stat1和Stat3在激活之前以稳定的同源二聚体形式存在。
