Crystal structure of a functional dimer of the PhoQ sensor domain.
Crystal structure of a functional dimer of the PhoQ sensor domain.
复制标题
PHOQ传感器结构域功能二聚体的晶体结构。
DOI：
10.1074/jbc.m710592200
复制
发表时间：
2008-05-16
影响因子：
4.8
通讯作者：
Waldburger, Carey D.
中科院分区：
文献类型：
--
作者：
Cheung, Jonah;Bingman, Craig A.;Reyngold, Marsha;Hendrickson, Wayne A.;Waldburger, Carey D.
Phop-PhoQ双组分系统是一个被广泛研究的细菌信号系统，它调节毒力和应激反应。组氨酸激酶传感器蛋白PhoQ的催化活性被细胞外低浓度的二价阳离子激活，随后响应调节因子Phop通过典型的磷酸转移途径被激活，这在这类系统中是典型的。肠道细菌的PhoQ感应域包含一个酸性残基簇(EDDDDAE)，它与二价阳离子直接结合。我们已经确定了野生型大肠杆菌PhoQ周质敏感区和一个突变变体的晶体结构，在突变变体中，酸性簇被中和为保守的不带电荷残基(QNNNNAQ)。PhoQ结构域的结构类似于DCU和CITA传感器结构域，并且该PhoQ-DCUS-CITA(PDC)传感器折叠被认为与表面上相似的PAS结构域折叠不同。对野生型结构的分析揭示了一种二聚体，它允许在Arg-50‘和Asp-179之间的二聚体界面上形成盐桥，并与酸性簇中的天冬氨酸残基结合。盐桥对体内PhoQ功能的生理重要性已被突变所证实。突变结构具有另一种非生理性的二聚体。
The PhoP-PhoQ two-component system is a well studied bacterial signaling system that regulates virulence and stress response. Catalytic activity of the histidine kinase sensor protein PhoQ is activated by low extracellular concentrations of divalent cations such as Mg2+, and subsequently the response regulator PhoP is activated in turn through a classic phosphotransfer pathway that is typical in such systems. The PhoQ sensor domains of enteric bacteria contain an acidic cluster of residues (EDDDDAE) that has been implicated in direct binding to divalent cations. We have determined crystal structures of the wild-type Escherichia coli PhoQ periplasmic sensor domain and of a mutant variant in which the acidic cluster was neutralized to conservative uncharged residues (QNNNNAQ). The PhoQ domain structure is similar to that of DcuS and CitA sensor domains, and this PhoQ-DcuS-CitA (PDC) sensor fold is seen to be distinct from the superficially similar PAS domain fold. Analysis of the wild-type structure reveals a dimer that allows for the formation of a salt bridge across the dimer interface between Arg-50′ and Asp-179 and with nickel ions bound to aspartate residues in the acidic cluster. The physiological importance of the salt bridge to in vivo PhoQ function has been confirmed by mutagenesis. The mutant structure has an alternative, non-physiological dimeric association.