Bilwes A M, Alex L A, Crane B R, Simon M I
Department of Biology, California Institute of Technology, Pasadena 91125, USA.
Cell. 1999 Jan 8;96(1):131-41. doi: 10.1016/s0092-8674(00)80966-6.
Histidine kinases allow bacteria, plants, and fungi to sense and respond to their environment. The 2.6 A resolution crystal structure of Thermotoga maritima CheA (290-671) histidine kinase reveals a dimer where the functions of dimerization, ATP binding, and regulation are segregated into domains. The kinase domain is unlike Ser/Thr/Tyr kinases but resembles two ATPases, Gyrase B and Hsp90. Structural analogies within this superfamily suggest that the P1 domain of CheA provides the nucleophilic histidine and activating glutamate for phosphotransfer. The regulatory domain, which binds the homologous receptor-coupling protein CheW, topologically resembles two SH3 domains and provides different protein recognition surfaces at each end. The dimerization domain forms a central four-helix bundle about which the kinase and regulatory domains pivot on conserved hinges to modulate transphosphorylation. Different subunit conformations suggest that relative domain motions link receptor response to kinase activity.
组氨酸激酶使细菌、植物和真菌能够感知并响应其环境。嗜热栖热菌CheA（290 - 671）组氨酸激酶分辨率为2.6埃的晶体结构显示出一个二聚体，其中二聚化、ATP结合和调节功能被分隔到不同结构域中。激酶结构域与丝氨酸/苏氨酸/酪氨酸激酶不同，但类似于两种ATP酶，即解旋酶B和热休克蛋白90。这个超家族中的结构相似性表明，CheA的P1结构域为磷酸转移提供亲核组氨酸和活化谷氨酸。结合同源受体偶联蛋白CheW的调节结构域，在拓扑结构上类似于两个SH3结构域，并在两端提供不同的蛋白质识别表面。二聚化结构域形成一个中央四螺旋束，激酶和调节结构域围绕该束在保守的铰链上转动，以调节转磷酸化。不同的亚基构象表明，相对的结构域运动将受体反应与激酶活性联系起来。
