Blackwell T K, Bowerman B, Priess J R, Weintraub H
Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science. 1994 Oct 28;266(5185):621-8. doi: 10.1126/science.7939715.
Maternally expressed Skn-1 protein is required for the correct specification of certain blastomere fates in early Caenorhabditis elegans embryos. Skn-1 contains a basic region similar to those of basic leucine zipper (bZIP) proteins but, paradoxically, it lacks a leucine zipper dimerization segment. Random sequence selection methods were used to show that Skn-1 binds to specific DNA sequences as a monomer. The Skn-1 basic region lies at the carboxyl terminus of an 85-amino acid domain that binds preferentially to a bZIP half-site and also recognizes adjacent 5' AT-rich sequences in the minor groove, apparently with an amino (NH2)-terminal "arm" related to those of homeodomain proteins. The intervening residues appear to stabilize interactions of these two subdomains with DNA. The Skn-1 DNA binding domain thus represents an alternative strategy for promoting binding of a basic region segment recognition helix to its cognate half-site. The results point to an underlying modularity in subdomains within established DNA binding domains.
母源表达的Skn-1蛋白对于秀丽隐杆线虫早期胚胎中某些卵裂球命运的正确特化是必需的。Skn-1含有一个与碱性亮氨酸拉链（bZIP）蛋白相似的碱性区域，但矛盾的是，它缺乏亮氨酸拉链二聚化区段。采用随机序列选择方法表明，Skn-1作为单体与特定DNA序列结合。Skn-1碱性区域位于一个85个氨基酸结构域的羧基末端，该结构域优先结合bZIP半位点，并且还识别小沟中相邻的5'富含AT的序列，显然是通过与同源结构域蛋白相关的氨基（NH2）末端“臂”来识别。中间的残基似乎稳定了这两个亚结构域与DNA的相互作用。因此，Skn-1 DNA结合结构域代表了一种促进碱性区域片段识别螺旋与其同源半位点结合的替代策略。结果表明，既定DNA结合结构域内的亚结构域存在潜在的模块化。
