Furukubo-Tokunaga K, Flister S, Gehring W J
Department of Cell Biology, Biozentrum der Universität Basel, Switzerland.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6360-4. doi: 10.1073/pnas.90.13.6360.
The segmental identity in animal development is determined by a set of homeotic selector genes clustered in the invertebrate HOM or vertebrate Hox homeo box complexes. These genes encode proteins with very similar homeodomains and highly diverged N- and C-terminal sequences. The Antennapedia (Antp) homeodomain, for instance, differs at only five amino acid positions from that of Sex combs reduced (Scr) protein. Using a heat shock assay in which chimeric Antp-Scr proteins are expressed ectopically in Drosophila, we have shown that the functional specificity of the Antp protein is determined by the four specific amino acids located in the flexible N-terminal arm of the homeodomain. The three-dimensional structure of the Antp homeodomain-DNA complex shows that this N-terminal arm is located in the minor groove of the DNA, suggesting that the functional specificity is determined either by slight differences in DNA binding and/or by selective interactions with other transcription factor(s).
动物发育过程中的节段身份由一组同源异型选择基因决定，这些基因聚集在无脊椎动物的HOM或脊椎动物的Hox同源异型框复合体中。这些基因编码的蛋白质具有非常相似的同源异型结构域以及高度分化的N端和C端序列。例如，触角足（Antp）的同源异型结构域与性梳减少（Scr）蛋白的同源异型结构域仅在五个氨基酸位置上有所不同。通过热休克实验，我们在果蝇中异位表达嵌合的Antp-Scr蛋白，结果表明Antp蛋白的功能特异性由位于同源异型结构域柔性N端臂上的四个特定氨基酸决定。Antp同源异型结构域与DNA复合体的三维结构显示，该N端臂位于DNA的小沟中，这表明功能特异性要么由DNA结合的细微差异决定，要么由与其他转录因子的选择性相互作用决定。
