6HCK

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

6HCK の概要

• エントリーDOI: 10.2210/pdb6hck/pdb
• 分子名称: Listeriolysin regulatory protein, LEUCINE, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: dna binding protein, prfa, listeria inhibition, dipeptide, virulence
• 由来する生物種: Listeria monocytogenes EGD-e
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55223.37

構造登録者

Grundstrom, C.,Oelker, M.,Krypotou, E.,Scortti, M.,Luisi, B.F.,Vazquez-Boland, J.,Sauer-Eriksson, A.E. (登録日: 2018-08-15, 公開日: 2019-02-13, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)