5eb2
Trp-bound YfiR
Structural highlights
FunctionYFIR_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 PubMedYfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the periplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal structures of YfiB alone and of an active mutant YfiBL43P complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiBL43P adopts a stretched conformation allowing activated YfiB to penetrate the peptidoglycan (PG) layer and access YfiR. YfiBL43P shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YfiB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YfiR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiBL43P-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system. Structural insights into the regulatory mechanism of the Pseudomonas aeruginosa YfiBNR system.,Xu M, Yang X, Yang XA, Zhou L, Liu TZ, Fan Z, Jiang T Protein Cell. 2016 Apr 25. PMID:27113583[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
