Schwartz C J, Sampson H M, Hlousek D, Percival-Smith A, Copeland J W, Simmonds A J, Krause H M
Banting and Best Department of Medical Research, University of Toronto and C.H.Best Institute, 112 College Street, Toronto, Ontario, Canada.
EMBO J. 2001 Feb 1;20(3):510-9. doi: 10.1093/emboj/20.3.510.
To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We also show that FTZ contains an AF2-interacting nuclear receptor box, the first to be found in a homeodomain protein. Both interaction motifs are shown to be necessary for physical interactions in vitro and for functional interactions in developing embryos. These unexpected findings have important implications for the conserved homologs of the two proteins.
为了激活转录，大多数核受体蛋白需要与它们的配体结合结构域（LBD）结合的共激活因子。果蝇FTZ因子1（FTZ-F1）蛋白是核受体超家族的一个保守成员，但之前被认为缺乏AF2基序，而AF2基序是配体和共激活因子结合所必需的。在这里，我们表明FTZ-F1确实具有AF2基序，并且它是结合共激活因子——含同源结构域的蛋白腹足缺刻蛋白（FTZ）所必需的。我们还表明FTZ含有一个与AF2相互作用的核受体框，这是在同源结构域蛋白中首次发现的。这两个相互作用基序对于体外的物理相互作用以及发育中的胚胎中的功能相互作用都是必需的。这些意外发现对这两种蛋白的保守同源物具有重要意义。
