6HCK

The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with dipeptide Leu-Leu

Summary for 6HCK

• Entry DOI: 10.2210/pdb6hck/pdb
• Descriptor: Listeriolysin regulatory protein, LEUCINE, SODIUM ION, ... (4 entities in total)
• Functional Keywords: dna binding protein, prfa, listeria inhibition, dipeptide, virulence
• Biological source: Listeria monocytogenes EGD-e
• Total number of polymer chains: 2
• Total formula weight: 55223.37

Authors

Grundstrom, C.,Oelker, M.,Krypotou, E.,Scortti, M.,Luisi, B.F.,Vazquez-Boland, J.,Sauer-Eriksson, A.E. (deposition date: 2018-08-15, release date: 2019-02-13, Last modification date: 2024-01-17)

Primary citation

Krypotou, E.,Scortti, M.,Grundstrom, C.,Oelker, M.,Luisi, B.F.,Sauer-Eriksson, A.E.,Vazquez-Boland, J.
Control of Bacterial Virulence through the Peptide Signature of the Habitat.
Cell Rep, 26:1815-1827.e5, 2019

PubMed Abstract: To 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.

PubMed: 30759392
DOI: 10.1016/j.celrep.2019.01.073

Experimental method

X-RAY DIFFRACTION (2.7 Å)