FUNCTIONAL SPECIFICITY OF THE ANTENNAPEDIA HOMEODOMAIN
FUNCTIONAL SPECIFICITY OF THE ANTENNAPEDIA HOMEODOMAIN
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DOI：
10.1073/pnas.90.13.6360
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发表时间：
1993-07-01
影响因子：
11.1
通讯作者：
GEHRING, WJ
中科院分区：
文献类型：
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作者：
FURUKUBOTOKUNAGA, K;FLISTER, S;GEHRING, WJ
动物发育中的节段性是由一组聚集在无脊椎动物HOM或脊椎动物Hox同源盒复合体中的同源异型选择基因决定的。这些基因编码具有非常相似的同源结构域和高度分歧的N-和C-末端序列的蛋白质。例如，Antp同源结构域与Scr蛋白只有5个氨基酸位置不同。使用热休克试验中嵌合Antp-Scr蛋白异位表达在果蝇，我们已经表明，Antp蛋白的功能特异性是由位于灵活的N-末端臂的同源结构域的四个特定的氨基酸。Antp同源结构域-DNA复合物的三维结构显示，该N-末端臂位于DNA的小沟中，表明功能特异性由DNA结合的微小差异和/或与其他转录因子的选择性相互作用决定。
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).