6hck
The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with dipeptide Leu-LeuThe Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with dipeptide Leu-Leu
Structural highlights
Function[PRFA_LISMO] Positively regulates expression of listeriolysin, of 1-phosphadidylinositol phosphodiesterase (PI-PLC) and other virulence factors. Publication Abstract from PubMedTo optimize fitness, pathogens selectively activate their virulence program upon host entry. Here, we report that the facultative intracellular bacterium Listeria monocytogenes exploits exogenous oligopeptides, a ubiquitous organic N source, to sense the environment and control the activity of its virulence transcriptional activator, PrfA. Using a genetic screen in adsorbent-treated (PrfA-inducing) medium, we found that PrfA is functionally regulated by the balance between activating and inhibitory nutritional peptides scavenged via the Opp transport system. Activating peptides provide essential cysteine precursor for the PrfA-inducing cofactor glutathione (GSH). Non-cysteine-containing peptides cause promiscuous PrfA inhibition. Biophysical and co-crystallization studies reveal that peptides inhibit PrfA through steric blockade of the GSH binding site, a regulation mechanism directly linking bacterial virulence and metabolism. L. monocytogenes mutant analysis in macrophages and our functional data support a model in which changes in the balance of antagonistic Opp-imported oligopeptides promote PrfA induction intracellularly and PrfA repression outside the host. Control of Bacterial Virulence through the Peptide Signature of the Habitat.,Krypotou E, Scortti M, Grundstrom C, Oelker M, Luisi BF, Sauer-Eriksson AE, Vazquez-Boland J Cell Rep. 2019 Feb 12;26(7):1815-1827.e5. doi: 10.1016/j.celrep.2019.01.073. PMID:30759392[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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