A cyclic di-GMP-binding adaptor protein interacts with histidine kinase to regulate two-component signaling
Yong, Grace Lisi
Date of Issue2016
School of Biological Sciences
Singapore Centre for Environmental Life Sciences Engineering
The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. In accordance with the role of SagS as a motile-sessile switch and biofilm growth factor, we show that HapZ impacts surface attachment and biofilm formation most likely by regulating the expression of a large number of genes. The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein.
Bacterial Signal Transduction
Journal of Biological Chemistry
© 2016 The American Society for Biochemistry and Molecular Biology, Inc. This paper was published in Journal of Biological Chemistry and is made available as an electronic reprint (preprint) with permission of The American Society for Biochemistry and Molecular Biology, Inc. The published version is available at: [http://dx.doi.org/10.1074/jbc.M116.73088]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.