Hirsch J A, Aggarwal A K
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
EMBO J. 1995 Dec 15;14(24):6280-91. doi: 10.1002/j.1460-2075.1995.tb00318.x.
even-skipped is a homeobox gene important in controlling segment patterning in the embryonic fruit fly. Its homeobox encodes a DNA binding domain which binds with similar affinities to two DNA consensus sequences, one AT-rich, the other GC-rich. We describe a crystallographic analysis of the Even-skipped homeodomain complexed to an AT-rich oligonucleotide at 2.0 A resolution. The structure reveals a novel arrangement of two homeodomains bound to one 10 bp DNA sequence in a tandem fashion. This arrangement suggests a mechanism for the homeoproteins' regulatory specificity. In addition, the functionally important residue Gln50 is observed in multiple conformations making direct and water-mediated hydrogen bonds with the DNA bases.
偶数跳基因是一种同源异型框基因，在控制果蝇胚胎的体节模式方面具有重要作用。其同源异型框编码一个DNA结合结构域，该结构域以相似的亲和力与两个DNA共有序列结合，一个富含AT，另一个富含GC。我们描述了偶数跳同源结构域与富含AT的寡核苷酸形成复合物的晶体学分析，分辨率为2.0埃。该结构揭示了两个同源结构域以串联方式与一个10 bp DNA序列结合的新排列方式。这种排列方式提示了同源蛋白调控特异性的一种机制。此外，在功能上重要的残基Gln50呈现出多种构象，与DNA碱基形成直接的和水介导的氢键。
