Banerjee-Basu S, Landsman D, Baxevanis A D
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
In Silico Biol. 1999;1(3):163-73.
The homeodomain is a common structural motif found in many transcription factors involved in cell fate determination during development. We have used threading analysis techniques to predict whether the atypical homeodomain of prospero (pros) family members could form the three-helical homeodomain structural motif, even though these proteins are not statistically similar to canonical homeodomains as assessed by BLAST searches. Amino acid sequences of these divergent homeodomain proteins were threaded through the X-ray coordinates of the Drosophila engrailed homeodomain protein [23]. The analysis confirms that the prospero class of homeodomain proteins is indeed capable of forming the homeodomain structure despite its low degree of sequence identity to the canonical homeodomain. Energy calculations indicate that the homeodomain structure is stabilized primarily by hydrophobic interactions between residues at the helical interfaces. Although the atypical prospero-type homeodomain shows very little sequence similarity when compared to other homeodomain proteins, the critical amino acids responsible for maintaining the three-dimensional structure are highly conserved. A number of other homeodomain proteins, such as PHO2p from Saccharomyces and Pax6 from human, were also included in the threading analysis and were shown to be able to form the engrailed structure, indicating that there are no rigid overall sequence requirements for the formation of the homeodomain structural motif. Based on the threading experiments and the subsequent structural alignment, a new amino acid signature that unambiguously identifies the prospero-type proteins was deduced.
同源异型结构域是一种常见的结构基序，存在于许多参与发育过程中细胞命运决定的转录因子中。我们使用穿线分析技术来预测prospero（pros）家族成员的非典型同源异型结构域是否能够形成三螺旋同源异型结构基序，尽管通过BLAST搜索评估，这些蛋白质在统计学上与典型同源异型结构域不相似。这些不同的同源异型结构域蛋白的氨基酸序列被穿线于果蝇成对控制基因同源异型结构域蛋白的X射线坐标[23]。分析证实，尽管prospero类同源异型结构域蛋白与典型同源异型结构域的序列同一性程度较低，但它确实能够形成同源异型结构。能量计算表明，同源异型结构主要通过螺旋界面处残基之间的疏水相互作用而稳定。尽管与其他同源异型结构域蛋白相比，非典型的prospero型同源异型结构域显示出很少的序列相似性，但负责维持三维结构的关键氨基酸是高度保守的。许多其他同源异型结构域蛋白，如酿酒酵母的PHO2p和人类的Pax6，也被纳入穿线分析，并显示能够形成成对控制基因结构，这表明形成同源异型结构基序没有严格的整体序列要求。基于穿线实验和随后的结构比对，推导了一种明确识别prospero型蛋白的新氨基酸特征。
