Atypical response regulator ChxR from Chlamydia trachomatis is structurally poised for DNA binding.
Atypical response regulator ChxR from Chlamydia trachomatis is structurally poised for DNA binding.
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DOI：
10.1371/journal.pone.0091760
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hefty PS
中科院分区：
文献类型：
--
作者：
Barta ML;Hickey JM;Anbanandam A;Dyer K;Hammel M;Hefty PS
ChxR是由专性细胞内细菌病原体沙眼衣原体编码的OmpR/PhoB亚家族的非典型双组分信号转导应答调节因子（RR）。尽管受体和效应子结构域与原型亚家族成员具有结构同源性，但ChxR不需要磷酸化来形成二聚体、DNA结合或转录激活。因此，我们假设ChxR是在有限的域间相互作用的DNA结合的最佳构象。为了解决这一假设，确定了ChxR效应结构域的NMR溶液结构，并与先前报道的ChxR受体结构域结构结合使用，以基于SAXS分析生成全长二聚体模型。小角度散射的ChxR支持最小的域间相互作用和效应域的构象，似乎只需要微妙的重定向最佳的大/小沟DNA相互作用的二聚体。SAXS模型也支持效应域是头-尾构象，与ChxR识别串联DNA重复序列一致。利用效应结构域结构来鉴定对于维持蛋白质-核酸相互作用至关重要的关键残基。结合先前对ChXR识别DNA的特定核苷酸的基本位置的分析，产生了与其同源顺式作用元件结合的全长ChXR二聚体的模型。
ChxR is an atypical two-component signal transduction response regulator (RR) of the OmpR/PhoB subfamily encoded by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Despite structural homology within both receiver and effector domains to prototypical subfamily members, ChxR does not require phosphorylation for dimer formation, DNA binding or transcriptional activation. Thus, we hypothesized that ChxR is in a conformation optimal for DNA binding with limited interdomain interactions. To address this hypothesis, the NMR solution structure of the ChxR effector domain was determined and used in combination with the previously reported ChxR receiver domain structure to generate a full-length dimer model based upon SAXS analysis. Small-angle scattering of ChxR supported a dimer with minimal interdomain interactions and effector domains in a conformation that appears to require only subtle reorientation for optimal major/minor groove DNA interactions. SAXS modeling also supported that the effector domains were in a head-to-tail conformation, consistent with ChxR recognizing tandem DNA repeats. The effector domain structure was leveraged to identify key residues that were critical for maintaining protein - nucleic acid interactions. In combination with prior analysis of the essential location of specific nucleotides for ChxR recognition of DNA, a model of the full-length ChxR dimer bound to its cognate cis-acting element was generated.
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