Structure of the Staphylococcus aureus AgrA LytTR domain bound to DNA reveals a beta fold with an unusual mode of binding
Structure of the Staphylococcus aureus AgrA LytTR domain bound to DNA reveals a beta fold with an unusual mode of binding
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DOI：
10.1016/j.str.2008.02.011
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发表时间：
2008-05-01
期刊：
影响因子：
5.7
通讯作者：
Stock, Ann M.
中科院分区：
文献类型：
--
作者：
Sidote, David J.;Barbieri, Christopher M.;Stock, Ann M.
LytTR结构域是在AlgR/AgrA/LytR转录因子家族中发现的DNA结合基序，其调节致病性细菌中的毒力因子和毒素基因表达。这个以前未表征的结构域与已知结构的蛋白质缺乏序列相似性。金黄色葡萄球菌AgrA与DNA十五聚体双链体复合的DNA结合结构域的晶体结构已在1.6埃分辨率下测定。该结构为LytTR结构域建立了一个10链的β折叠，并揭示了其与DNA相互作用的模式。AgrA环区内的残基接触寡核苷酸双链体一面上的两个连续的大沟和间插的小沟，诱导DNA中的显著弯曲。AgrA中关键相互作用残基取代后DNA结合的丧失支持了观察到的结合模式。这种蛋白质-DNA相互作用的模式为未来的抗微生物药物设计提供了潜在的靶点。
The LytTR domain is a DNA-binding motif found within the AlgR/AgrA/LytR family of transcription factors that regulate virulence factor and toxin gene expression in pathogenic bacteria. This previously uncharacterized domain lacks sequence similarity with proteins of known structure. The crystal structure of the DNA-binding domain of Staphylococcus aureus AgrA complexed with a DNA pentadecamer duplex has been determined at 1.6 angstrom resolution. The structure establishes a 10-stranded beta fold for the LytTR domain and reveals its mode of interaction with DNA. Residues within loop regions of AgrA contact two successive major grooves and the intervening minor groove on one face of the oligonucleotide duplex, inducing a substantial bend in the DNA. Loss of DNA binding upon substitution of key interacting residues in AgrA supports the observed binding mode. This mode of protein-DNA interaction provides a potential target for future antimicrobial drug design.