一种新的 DNA 结合域结构，调节多种真菌的发病机制。
Structure of a new DNA-binding domain which regulates pathogenesis in a wide variety of fungi.
机构信息
Departments of Microbiology and Immunology and.
Departments of Microbiology and Immunology andDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94158.
出版信息
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10404-10. doi: 10.1073/pnas.1410110111. Epub 2014 Jul 3.
WOPR-domain proteins are found throughout the fungal kingdom where they function as master regulators of cell morphology and pathogenesis. Genetic and biochemical experiments previously demonstrated that these proteins bind to specific DNA sequences and thereby regulate transcription. However, their primary sequence showed no relationship to any known DNA-binding domain, and the basis for their ability to recognize DNA sequences remained unknown. Here, we describe the 2.6-Å crystal structure of a WOPR domain in complex with its preferred DNA sequence. The structure reveals that two highly conserved regions, separated by an unconserved linker, form an interdigitated β-sheet that is tilted into the major groove of DNA. Although the main interaction surface is in the major groove, the highest-affinity interactions occur in the minor groove, primarily through a deeply penetrating arginine residue. The structure reveals a new, unanticipated mechanism by which proteins can recognize specific sequences of DNA.
WOPR 结构域蛋白在真菌界中广泛存在，它们作为细胞形态和发病机制的主调控因子发挥作用。遗传和生化实验先前表明，这些蛋白质与特定的 DNA 序列结合，从而调节转录。然而，它们的一级序列与任何已知的 DNA 结合结构域都没有关系，它们识别 DNA 序列的基础仍然未知。在这里，我们描述了 WOPR 结构域与它的首选 DNA 序列的 2.6Å 晶体结构。该结构揭示了两个高度保守的区域，由不保守的连接子隔开，形成一个交错的 β-折叠，倾斜进入 DNA 的大沟。尽管主要的相互作用表面在大沟中，但最高亲和力的相互作用发生在小沟中，主要通过一个深穿透的精氨酸残基。该结构揭示了一种新的、意想不到的机制，蛋白质可以识别特定的 DNA 序列。
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