| Structural highlights
Function
YFIR_PSEAE Negatively regulates the activity of the diguanylate cyclase TpbB/YfiN, leading to decreased c-di-GMP production (PubMed:20300602). Inhibits TpbB/YfiN allosterically, through a hydrophobic interaction between the C-terminus of YfiR and a conserved region of the periplasmic PAS domain of TpbB/YfiN (PubMed:22719254). Under reducing conditions, may also act as an YfiB-independent sensing device that is able to activate TpbB/YfiN in response to the redox status of the periplasm (PubMed:22719254).[1] [2] Part of the YfiB-TpbB-YfiR (or yfiBNR) system, encoding a tripartite signaling module that modulates intracellular c-di-GMP levels (PubMed:20300602, PubMed:22719254). The system is a key regulator of the small colony variant (SCV) phenotype, and plays an important role in biofilm formation and in vivo persistence (PubMed:20300602). The c-di-GMP produced by TpbB/YfiN stimulates the production of the Pel and Psl exopolysaccharides, which promotes surface attachment, generates an SCV phenotype and confers resistance against phagocytosis (PubMed:20300602).[3] [4]
Publication Abstract from PubMed
YfiBNR, a tripartite cyclic-di-GMP (c-di-GMP) signalling system, plays an important role in biofilm formation of the gram-negative bacterium P. aeruginosa, which regulates the cellular processes strongly associated with chronic lung infections and drug resistance. The outer-membrane lipoprotein YfiB can release the inhibition of the inner membrane protein YfiR by sequestering the periplasmatic protein YfiR, resulting in the activation of diguanylate cyclase activity of YfiN and the production of c-di-GMP. In contrast to the extensive studies on c-di-GMP, little is known about how GMP acts in the YfiBNR system. Here, we report the crystal structures of YfiR complexed with GMP and YfiBL43P-YfiR complexed with GMP. In the YfiR-GMP complex, GMP is located in a hydrophilic pocket formed by R175/H177/R60, while in the YfiBL43P-YfiR-GMP complex, GMP is located in a slightly separated hydrophilic pocket, with GMP forming hydrogen bonds with both YfiB and YfiR. A binding affinity test and biofilm formation assay indicated that GMP may activate diguanylate cyclase activity to promote biofilm production by promoting the affinity of YfiB and YfiR. This finding thus provides a new perspective for preventing biofilm-related antibiotic resistance and chronic infections.
Structural insights into the functional role of GMP in modulating the YfiBNR system.,Zhou L, Xu M, Jiang T Biochem Biophys Res Commun. 2017 Sep 1. pii: S0006-291X(17)31661-3. doi:, 10.1016/j.bbrc.2017.08.139. PMID:28870806[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Malone JG, Jaeger T, Spangler C, Ritz D, Spang A, Arrieumerlou C, Kaever V, Landmann R, Jenal U. YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa. PLoS Pathog. 2010 Mar 12;6(3):e1000804. PMID:20300602 doi:10.1371/journal.ppat.1000804
- ↑ Malone JG, Jaeger T, Manfredi P, Dötsch A, Blanka A, Bos R, Cornelis GR, Häussler S, Jenal U. The YfiBNR signal transduction mechanism reveals novel targets for the evolution of persistent Pseudomonas aeruginosa in cystic fibrosis airways. PLoS Pathog. 2012;8(6):e1002760. PMID:22719254 doi:10.1371/journal.ppat.1002760
- ↑ Malone JG, Jaeger T, Spangler C, Ritz D, Spang A, Arrieumerlou C, Kaever V, Landmann R, Jenal U. YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa. PLoS Pathog. 2010 Mar 12;6(3):e1000804. PMID:20300602 doi:10.1371/journal.ppat.1000804
- ↑ Malone JG, Jaeger T, Manfredi P, Dötsch A, Blanka A, Bos R, Cornelis GR, Häussler S, Jenal U. The YfiBNR signal transduction mechanism reveals novel targets for the evolution of persistent Pseudomonas aeruginosa in cystic fibrosis airways. PLoS Pathog. 2012;8(6):e1002760. PMID:22719254 doi:10.1371/journal.ppat.1002760
- ↑ Zhou L, Xu M, Jiang T. Structural insights into the functional role of GMP in modulating the YfiBNR system. Biochem Biophys Res Commun. 2017 Sep 1. pii: S0006-291X(17)31661-3. doi:, 10.1016/j.bbrc.2017.08.139. PMID:28870806 doi:http://dx.doi.org/10.1016/j.bbrc.2017.08.139
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