PDF(Pubmed)
Abstract：
Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a bacterial second messenger that modulates various processes including biofilm formation, motility, and host-microbe symbiosis. Numerous studies have conducted comprehensive analysis of c-di-GMP. However, the mechanisms by which certain environmental signals such as iron control intracellular c-di-GMP levels are unclear. Here, we show that iron regulates c-di-GMP levels in Pseudomonas aeruginosa by modulating the interaction between an iron-sensing protein, IsmP, and a diguanylate cyclase, ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the IsmP-ImcA interaction, which leads to increased c-di-GMP synthesis by ImcA, thus promoting biofilm formation and reducing bacterial motility. Structural characterization of the apo-CHASE4 domain and its binding to iron allows us to pinpoint residues defining its specificity. In addition, the cryo-electron microscopy structure of ImcA in complex with a c-di-GMP analog (GMPCPP) suggests a unique conformation in which the compound binds to the catalytic pockets and to the membrane-proximal side located at the cytoplasm. Thus, our results indicate that a CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes.
摘要：
环二聚磷酸鸟苷（c-di-GMP）作为细菌第二信使，调节各种过程，包括生物膜的形成，运动性,和宿主-微生物共生。大量研究对c-di-GMP进行了全面分析。然而,某些环境信号如铁控制细胞内c-di-GMP水平的机制尚不清楚.这里,我们表明，铁调节c-di-GMP水平在铜绿假单胞菌通过调节之间的相互作用的铁敏感蛋白，IsMP,还有一种双鸟苷酸环化酶,伊姆卡.铁与IsmP的CHASE4结构域的结合抑制IsmP-ImcA相互作用，这导致ImcA的c-di-GMP合成增加，从而促进生物膜形成和降低细菌运动性。apo-CHASE4结构域的结构表征及其与铁的结合使我们能够精确定位定义其特异性的残基。此外,ImcA与c-di-GMP类似物（GMPCPP）复合的低温电子显微镜结构表明，该化合物具有独特的构象，其中该化合物与催化袋和位于细胞质的膜近端侧结合。因此，我们的结果表明，CHASE4结构域直接感知铁并调节c-di-GMP代谢酶之间的串扰。
