Lee Vincent T, Matewish Jody M, Kessler Jennifer L, Hyodo Mamoru, Hayakawa Yoshihiro, Lory Stephen
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mol Microbiol. 2007 Sep;65(6):1474-84. doi: 10.1111/j.1365-2958.2007.05879.x.
Bis-(3',5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c-di-GMP signal transduction, including recognition of c-di-GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c-di-GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c-di-GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c-di-GMP receptor that mediates c-di-GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c-di-GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c-di-GMP. The combination of a c-di-GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide.
双（3'，5'）-环二聚鸟苷单磷酸（c-di-GMP）已被证明是一种全局调节分子，可调节细菌的相互反应，以激活毒力途径或生物膜形成。c-di-GMP信号转导的机制，包括对c-di-GMP的识别以及随后的表型调节，在很大程度上仍未得到充分表征。这些调节途径的关键成分是各种衔接蛋白（c-di-GMP受体）。有令人信服的证据表明，除了PilZ结构域外，还有其他未鉴定的c-di-GMP受体。在这里，我们表明铜绿假单胞菌的PelD蛋白是一种新型的c-di-GMP受体，可介导c-di-GMP对PEL多糖生物合成的调节。对PelD直系同源物的分析确定了一些c-di-GMP结合以及PEL多糖合成所需的保守残基。PelD与二鸟苷酸环化酶抑制位点的二级结构相似性表明，一个共同的折叠结构可以作为结合c-di-GMP的平台。在一个蛋白质结构域内，c-di-GMP结合位点与各种输出信号基序的组合，为不同细胞对这种调节性二核苷酸的反应特异性提供了解释。
