8CBP

The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with tetrapeptide Thr-Glu-Pro-Leu

8CBP の概要

• エントリーDOI: 10.2210/pdb8cbp/pdb
• 分子名称: Listeriolysin regulatory protein, peptide THR-GLU-PRO-LEU (3 entities in total)
• 機能のキーワード: dna binding protein, prfa, listeria inhibition, virulence, transcription
• 由来する生物種: Listeria monocytogenes; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 55373.55

構造登録者

Hainzl, T.,Oelker, M.,Sauer-Eriksson, A.E. (登録日: 2023-01-25, 公開日: 2024-08-07, 最終更新日: 2025-03-12)

主引用文献

Hainzl, T.,Scortti, M.,Lindgren, C.,Grundstrom, C.,Krypotou, E.,Vazquez-Boland, J.A.,Sauer-Eriksson, A.E.
Structural basis of promiscuous inhibition of Listeria virulence activator PrfA by oligopeptides.
Cell Rep, 44:115290-115290, 2025

PubMed Abstract: The facultative pathogen Listeria monocytogenes uses a master regulator, PrfA, to tightly control the fitness-costly expression of its virulence factors. We found that PrfA activity is repressed via competitive occupancy of the binding site for the PrfA-activating cofactor, glutathione, by exogenous nutritional oligopeptides. The inhibitory peptides show different sequence and physicochemical properties, but how such a wide variety of oligopeptides can bind PrfA was unclear. Using crystal structure analysis of PrfA complexed with inhibitory tri- and tetrapeptides, we show here that the binding promiscuity is due to the ability of PrfA β5 in the glutathione-binding inter-domain tunnel to establish parallel or antiparallel β sheet-like interactions with the peptide backbone. Spacious tunnel pockets provide additional flexibility for unspecific peptide accommodation while providing selectivity for hydrophobic residues. Hydrophobic contributions from two adjacent peptide residues appear to be critical for efficient PrfA inhibitory binding. In contrast to glutathione, peptide binding prevents the conformational change required for the correct positioning of the DNA-binding helix-turn-helix motifs of PrfA, effectively inhibiting virulence gene expression.

PubMed: 39970044
DOI: 10.1016/j.celrep.2025.115290

実験手法

X-RAY DIFFRACTION (2.7 Å)