A cyclic di-GMP-binding adaptor protein interacts with histidine kinase to regulate two-component signaling

• Main Authors: Xu, Linghui, Venkataramani, Prabhadevi, Ding, Yichen, Liu, Yang, Deng, Yinyue, Yong, Grace Lisi, Xin, Lingyi, Ye, Ruijuan, Zhang, Lianhui, Yang, Liang, Liang, Zhao-Xun
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2018
• Subjects: DRNTU::Science::Biological sciences; Biofilm; Bacterial Signal Transduction
• Online Access: https://hdl.handle.net/10356/89409; http://hdl.handle.net/10220/46264
• Institution: Nanyang Technological University

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.