Structural Basis and Target-specific Modulation of ADP Sensing by the Synechococcus elongatus PII Signaling Protein*
Structural Basis and Target-specific Modulation of ADP Sensing by the Synechococcus elongatus PII Signaling Protein*
复制标题
细长聚球藻 PII 信号蛋白对 ADP 传感的结构基础和目标特异性调节*
DOI：
10.1074/jbc.m113.536557
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
K. Forchhammer
中科院分区：
文献类型：
--
作者：
K. Zeth;Oleksandra Fokina;K. Forchhammer
背景：高度保守的PII信号蛋白监测碳/氮平衡和能量状态。结果：同源三聚体细长聚球藻PII与ADP的晶体揭示了ADP抗协同结合的结构基础。与PipX受体的相互作用改变了PII的ATP/ADP偏好性。结论：PII信号受受体蛋白的构象状态调节。意义：分子信息是通过蛋白质结构的可塑性来处理的。PII信号传导蛋白是自然界中最通用的信号传导装置之一，具有高度保守的结构。在蓝藻中，PipX和N-乙酰基-L-谷氨酸激酶是PII信号的受体，并且这些相互作用由ADP、ATP和2-酮戊二酸调节。这些效应分子相互依赖地结合三聚体PII蛋白上的三个抗协同结合位点，从而影响其结构。在这里，我们使用的PII蛋白从细长聚球藻PCC 7942，以揭示抗合作ADP结合的结构基础。此外，我们阐明了PI I-受体相互作用和ATP/ADP比率传感的相互影响。两种形式的三聚体PII的晶体结构，一个ADP结合和其他所有三个ADP结合位点被占用，揭示了ADP结合模式的显着差异：在一个网站（S1）ADP是通过侧链和主链相互作用紧密结合，而在其他两个网站（S2和S3）的ADP分子仅结合的主链相互作用。在存在PII受体PipX的情况下，ADP对第一结合位点S1的亲和力强烈增加，而对ATP的亲和力由于PipX有利于PII-ADP的S1构象而降低。因此，PII-PipX相互作用对ATP/ADP比率的细微波动高度敏感。相比之下，PII-N-乙酰基-1-谷氨酸激酶相互作用，这是由ADP的负面影响，是不敏感的这些波动。通过其受体调节PII的代谢物感测特性允许PII以靶特异性方式差异地感知信号并执行多任务信号转导。
Background: Highly conserved PII signaling proteins monitor carbon/nitrogen balance and energy status. Results: Crystals of homotrimeric Synechococcus elongatus PII with ADP reveal the structural basis of anti-cooperative ADP binding. Interaction with PipX receptor changes the ATP/ADP preference of PII. Conclusion: PII signaling is modulated by conformational states imposed by the receptor protein. Significance: Molecular information is processed through protein structure plasticity. PII signaling proteins comprise one of the most versatile signaling devices in nature and have a highly conserved structure. In cyanobacteria, PipX and N-acetyl-l-glutamate kinase are receptors of PII signaling, and these interactions are modulated by ADP, ATP, and 2-oxoglutarate. These effector molecules bind interdependently to three anti-cooperative binding sites on the trimeric PII protein and thereby affect its structure. Here we used the PII protein from Synechococcus elongatus PCC 7942 to reveal the structural basis of anti-cooperative ADP binding. Furthermore, we clarified the mutual influence of PII-receptor interaction and sensing of the ATP/ADP ratio. The crystal structures of two forms of trimeric PII, one with one ADP bound and the other with all three ADP-binding sites occupied, revealed significant differences in the ADP binding mode: at one site (S1) ADP is tightly bound through side-chain and main-chain interactions, whereas at the other two sites (S2 and S3) the ADP molecules are only bound by main-chain interactions. In the presence of the PII-receptor PipX, the affinity of ADP to the first binding site S1 strongly increases, whereas the affinity for ATP decreases due to PipX favoring the S1 conformation of PII-ADP. In consequence, the PII-PipX interaction is highly sensitive to subtle fluctuations in the ATP/ADP ratio. By contrast, the PII-N-acetyl-l-glutamate kinase interaction, which is negatively affected by ADP, is insensitive to these fluctuations. Modulation of the metabolite-sensing properties of PII by its receptors allows PII to differentially perceive signals in a target-specific manner and to perform multitasking signal transduction.
影响因子：
5.6
作者：
Fokina, Oleksandra;Chellamuthu, Vasuki-Ranjani;Forchhammer, Karl
通讯作者：
Forchhammer, Karl