Wilson D S, Guenther B, Desplan C, Kuriyan J
Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA.
Cell. 1995 Sep 8;82(5):709-19. doi: 10.1016/0092-8674(95)90468-9.
The crystal structure of the paired homeodomain bound to DNA as a cooperative dimer has been determined to 2.0 A resolution. Direct contacts between each homeodomain and the DNA are similar to those described previously. In addition, an extensive network of water molecules mediates contacts between the recognition helix and the DNA major groove. Several symmetrical contacts between the two homeodomains underlie the cooperative interaction, and deformations in the DNA structure are necessary for the establishment of these contacts. Comparison with structures of homeodomains bound monomerically to DNA suggests that the binding of a single paired homeodomain can introduce these DNA distortions, thus preparing a template for the cooperative interaction with a second homeodomain. This study shows how the paired (Pax) class homeodomains have achieved cooperativity in DNA binding without the assistance of other domains, thereby enabling the recognition of target sequences that are long enough to ensure specificity.
已确定与 DNA 结合形成协同二聚体的配对同源结构域的晶体结构，分辨率为 2.0 Å。每个同源结构域与 DNA 之间的直接接触与先前描述的相似。此外，广泛的水分子网络介导了识别螺旋与 DNA 大沟之间的接触。两个同源结构域之间的几个对称接触是协同相互作用的基础，DNA 结构的变形对于建立这些接触是必要的。与单体结合到 DNA 的同源结构域结构的比较表明，单个配对同源结构域的结合可以引入这些 DNA 扭曲，从而为与第二个同源结构域的协同相互作用准备一个模板。这项研究表明，配对（Pax）类同源结构域如何在没有其他结构域协助的情况下实现 DNA 结合的协同性，从而能够识别足够长以确保特异性的靶序列。
