一个衍生的变构开关是 HOXA11 和 FOXO1 之间条件协同性进化的基础。
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1.
机构信息
Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
Departments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
出版信息
Cell Rep. 2016 Jun 7;15(10):2097-2108. doi: 10.1016/j.celrep.2016.04.088. Epub 2016 May 26.
Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.
转录因子（TFs）在发育过程中发挥多种作用。鉴于这种多功能性，人们一直认为 TFs 在进化上受到高度限制。在这里，我们研究了两个 TFs，HOXA11 和 FOXO1 之间衍生功能相互作用起源的分子机制。我们之前已经表明，HOXA11 在哺乳动物子宫内膜基质细胞中的调节作用需要与 FOXO1 相互作用，并且这些蛋白质之间的物理相互作用先于其功能协同作用而进化。在这里，我们证明了 HOXA11 和 FOXO1 之间衍生的功能协同作用是由于 FOXO1 对 HOXA11 的衍生变构调节。这项研究表明，TF 功能可以通过影响先前存在的蛋白质复合物的功能输出的变化而进化。
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