title: A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling.
abstract: 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.
authors.affiliation: From the School of Biological Sciences and Guangdong Innovative and Entrepreneurial Research Team of Sociomicrobiology Basic Science and Frontier Technology and.
authors.forename: Linghui
authors.initials: L
authors.lastname: Xu
authors.affiliation: From the School of Biological Sciences and.
authors.forename: Prabhadevi
authors.initials: P
authors.lastname: Venkataramani
authors.affiliation: From the School of Biological Sciences and Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 and.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Innovative and Entrepreneurial Research Team of Sociomicrobiology Basic Science and Frontier Technology and.
authors.forename: Yinyue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: From the School of Biological Sciences and.
authors.forename: Grace Lisi
authors.initials: GL
authors.lastname: Yong
authors.affiliation: From the School of Biological Sciences and.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Xin
authors.affiliation: From the School of Biological Sciences and.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Ye
authors.affiliation: Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, People's Republic of China.
authors.forename: Lianhui
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the School of Biological Sciences and Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 and yangliang@ntu.edu.sg.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: From the School of Biological Sciences and zxliang@ntu.edu.sg.
authors.forename: Zhao-Xun
authors.initials: ZX
authors.lastname: Liang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C097615:PilZ protein, Pseudomonas aeruginosa; C062025:bis(3',5')-cyclic diguanylic acid; D000071677:Histidine Kinase; D006152:Cyclic GMP
keywords: Pseudomonas aeruginosa (P. aeruginosa); bacterial signal transduction; biofilm; cyclic di-GMP (c-di-GMP); histidine kinase