Branched Signal Wiring of an Essential Bacterial Cell-Cycle Phosphotransfer Protein
Branched Signal Wiring of an Essential Bacterial Cell-Cycle Phosphotransfer Protein
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DOI：
10.1016/j.str.2013.06.024
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发表时间：
2013-09-03
期刊：
影响因子：
5.7
通讯作者：
Shapiro, Lucy
中科院分区：
文献类型：
--
作者：
Blair, Jimmy A.;Xu, Qingping;Shapiro, Lucy
细胞信号的忠实传播对细菌的生存至关重要，在新月柄杆菌中，ChpT是细胞周期回路中的重要介质。ChpT作为一种含组氨酸的磷酸转移蛋白（HPt）发挥作用，将磷酰基从CckA的受体结构域（上游杂合组氨酸激酶（HK））转运至控制细胞周期进程的两种下游反应调节因子（CtrA或CpdR）之一。为了了解ChpT如何与多种信号伴侣相互作用，我们以2.3埃分辨率解析了ChpT的晶体结构。ChpT采用伪HK结构，但不结合ATP。我们确定了两个点突变类影响磷酸转移和细胞形态：一个是全局损害ChpT磷酸转移，第二个介导的合作伙伴选择。重要的是，一小组保守的ChpT残基促进信号传导串扰，并有助于激活主调节因子CtrA的分支信号传导，同时使CtrA降解信号CpdR失活。
Vital to bacterial survival is the faithful propagation of cellular signals, and in Caulobacter crescentus, ChpT is an essential mediator within the cell-cycle circuit. ChpT functions as a histidine-containing phosphotransfer protein (HPt) that shuttles a phosphoryl group from the receiver domain of CckA, the upstream hybrid histidine kinase (HK), to one of two downstream response regulators (CtrA or CpdR) that controls cell-cycle progression. To understand how ChpT interacts with multiple signaling partners, we solved the crystal structure of ChpT at 2.3 angstrom resolution. ChpT adopts a pseudo-HK architecture but does not bind ATP. We identified two point mutation classes affecting phosphotransfer and cell morphology: one that globally impairs ChpT phosphotransfer, and a second that mediates partner selection. Importantly, a small set of conserved ChpT residues promotes signaling crosstalk and contributes to the branched signaling that activates the master regulator CtrA while inactivating the CtrA degradation signal, CpdR.