Vershon A K, Johnson A D
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Cell. 1993 Jan 15;72(1):105-12. doi: 10.1016/0092-8674(93)90054-t.
Homeodomains are folded into a characteristic three-dimensional structure capable of recognizing DNA in a sequence-specific manner. We show that correct target site selection by the yeast alpha 2 protein requires, as well as its homeodomain, an adjacent short and apparently unstructured region of the protein. This flexible homeodomain extension is responsible for specifying an interaction with a second regulatory protein, MCM1, which permits the cooperative binding of the two proteins to an operator. Two additional experiments suggest that this extension-homeodomain arrangement is likely to have some generality. First, when the extension of alpha 2 is grafted onto the Drosophila engrailed homeodomain, it yields a protein with the DNA binding specificity of engrailed and the ability to bind cooperatively to DNA with MCM1. Second, the alpha 2 extension specifies interaction not only with the yeast MCM1 protein, but also with the related human protein SRF.
同源结构域折叠成一种独特的三维结构，能够以序列特异性的方式识别DNA。我们发现，酵母α2蛋白正确选择靶位点不仅需要其同源结构域，还需要该蛋白相邻的一个短的、看似无结构的区域。这种灵活的同源结构域延伸负责指定与另一种调节蛋白MCM1的相互作用，从而使这两种蛋白能够协同结合到一个操纵基因上。另外两个实验表明，这种延伸-同源结构域的排列方式可能具有一定的普遍性。首先，当将α2的延伸区域嫁接到果蝇成对控制基因的同源结构域上时，会产生一种具有成对控制基因DNA结合特异性且能与MCM1协同结合DNA的蛋白。其次，α2的延伸区域不仅指定了与酵母MCM1蛋白的相互作用，还指定了与相关的人类蛋白SRF的相互作用。
