Helix bundle loops determine whether histidine kinases autophosphorylate in cis or in trans.
Helix bundle loops determine whether histidine kinases autophosphorylate in cis or in trans.
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DOI：
10.1016/j.jmb.2013.01.011
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发表时间：
2013-04-12
影响因子：
5.6
通讯作者：
Laub, Michael T.
中科院分区：
文献类型：
--
作者：
Ashenberg, Orr;Keating, Amy E.;Laub, Michael T.
细菌经常使用双组分信号转导途径来感知和响应环境和细胞内刺激。在接受刺激后，同型二聚体传感器组氨酸激酶自磷酸化，然后将其磷酰基转移到同源反应调节剂。据报道，组氨酸激酶的自磷酸化以顺式和反式两种形式发生，但决定采用哪种机制的分子决定因素尚不清楚。基于结构上的考虑，一种模型假定螺旋二聚化结构域底部的环的手性起关键作用。在这里，我们通过替换E中的循环来测试这个模型。coliEnvZ，其反式自磷酸化，具有来自顺式自磷酸化的三个PhoR直向同源物的环。这些嵌合激酶顺式自磷酸化，表明这个小环足以确定自磷酸化机制。此外，我们报告说，自磷酸化的机制是保守的组氨酸激酶的邻位组，尽管高度不同的环序列。这些发现表明，组氨酸激酶是在选择性压力下，以保持其模式的自磷酸化，但可以这样做的范围很广的序列。
Bacteria frequently use two-component signal transduction pathways to sense and respond to environmental and intracellular stimuli. Upon receipt of a stimulus, a homodimeric sensor histidine kinase autophosphorylates and then transfers its phosphoryl group to a cognate response regulator. The autophosphorylation of histidine kinases has been reported to occur both in cis and in trans, but the molecular determinants dictating which mechanism is employed are unknown. Based on structural considerations, one model posits that the handedness of a loop at the base of the helical dimerization domain plays a critical role. Here, we tested this model by replacing the loop from E. coli EnvZ, which autophosphorylates in trans, with the loop from three PhoR orthologs that autophosphorylate in cis. These chimeric kinases autophosphorylated in cis, indicating that this small loop is sufficient to determine autophosphorylation mechanism. Further, we report that the mechanism of autophosphorylation is conserved in orthologous sets of histidine kinases, despite highly dissimilar loop sequences. These findings suggest that histidine kinases are under selective pressure to maintain their mode of autophosphorylation, but can do so with a wide range of sequences.
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