Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein
Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein
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DOI：
10.1038/sj.emboj.7600886
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发表时间：
2005-12-21
期刊：
影响因子：
11.4
通讯作者：
Hendrickson, WA
中科院分区：
文献类型：
--
作者：
Marina, A;Waldburger, CD;Hendrickson, WA
绝大多数组氨酸激酶（HK）是具有自激酶、磷酸转移和磷酸酶活性的多功能酶，其中大多数是跨膜传感器蛋白。传感器 HK 具有保守的细胞质磷酸化和 ATP 结合激酶结构域。不同的酶活性需要这些域之一或两个的参与，这意味着需要不同的构象状态。催化结构域通过卷曲螺旋片段与膜连接，有时还包括其他结构域。我们在这里描述了传感器 HK 完整细胞质区域的第一个晶体结构，该结构来自嗜热栖热袍菌与 ADP beta N 的复合物，分辨率为 1.9 埃。该结构揭示了几个保守残基先前未识别的功能，并揭示了似乎准备进行磷酸转移的状态下结构域的相对配置。因此，该结构激发了对自磷酸化、磷酸转移和反应调节器去磷酸化以及通过卷曲螺旋片段的信号转导机制的假设。突变测试支持域间接触的功能相关性。
The large majority of histidine kinases (HKs) are multifunctional enzymes having autokinase, phosphotransfer and phosphatase activities, and most of these are transmembrane sensor proteins. Sensor HKs possess conserved cytoplasmic phosphorylation and ATP-binding kinase domains. The different enzymatic activities require participation by one or both of these domains, implying the need for different conformational states. The catalytic domains are linked to the membrane through a coiled-coil segment that sometimes includes other domains. We describe here the first crystal structure of the complete cytoplasmic region of a sensor HK, one from the thermophile Thermotoga maritima in complex with ADP beta N at 1.9 angstrom resolution. The structure reveals previously unidentified functions for several conserved residues and reveals the relative disposition of domains in a state seemingly poised for phosphotransfer. The structure thereby inspires hypotheses for the mechanisms of autophosphorylation, phosphotransfer and response-regulator dephosphorylation, and for signal transduction through the coiled-coil segment. Mutational tests support the functional relevance of interdomain contacts.