Listeriosis is one of the most serious foodborne diseases caused by the intracellular bacterium Listeria monocytogenes. Its two major virulence factors, broad-range phospholipase C (LmPC-PLC) and the pore-forming toxin listeriolysin O (LLO), enable the bacterium to spread in the host by destroying cell membranes. Here, we determine the crystal structure of LmPC-PLC and complement it with the functional analysis of this enzyme. This reveals that LmPC-PLC has evolved several structural features to regulate its activity, including the invariant position of the N-terminal tryptophan (W1), the structurally plastic active site, Zn-dependent activity, and the tendency to form oligomers with impaired enzymatic activity. We demonstrate that the enzymatic activity of LmPC-PLC can be specifically inhibited by its propeptide added in trans. Furthermore, we show that the phospholipase activity of LmPC-PLC facilitates the pore-forming activity of LLO and affects the morphology of LLO oligomerization on lipid membranes, revealing the multifaceted synergy of the two virulence factors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576769 | PMC |
| http://dx.doi.org/10.1038/s41467-023-42134-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Comparative Analysis of Different Strains Reveals a Virulent Factor, Cyclic Pro-Phe, Using a Differential Expression Profile Analysis of Non-Ribosomal Peptide Synthetases.
Insects
September 2024
Department of Plant Medicals, Andong National University, Andong 36729, Republic of Korea.
Entomopathogenic bacteria, classified into the genus , exhibit a dual lifestyle as mutualistic symbionts to nematodes and as pathogens to a broad range of insects. Bacterial virulence depends on toxin proteins that induce toxemia and various immunosuppressive secondary metabolites that cause septicemia. Particularly, the immunosuppressive properties of bacteria determine the variability of their insecticidal activities.
View Article and Find Full Text PDFUntangling the role of RhoA in the heart: protective effect and mechanism.
Cell Death Dis
August 2024
Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093-0636, USA.
RhoA (ras homolog family member A) is a small G-protein that transduces intracellular signaling to regulate a broad range of cellular functions such as cell growth, proliferation, migration, and survival. RhoA serves as a proximal downstream effector of numerous G protein-coupled receptors (GPCRs) and is also responsive to various stresses in the heart. Upon its activation, RhoA engages multiple downstream signaling pathways.
View Article and Find Full Text PDFComprehensive identification and functional characterization of GhpPLA gene family in reproductive organ development.
BMC Plant Biol
November 2023
National Engineering Research Center of Cotton Biology Breeding and Industrial Technology, Institute of Cotton Research, Chinese Academy of Agricultural Science, Anyang, Henan, 455000, China.
Background: Phospholipases As (PLAs) are acyl hydrolases that catalyze the release of free fatty acids in phospholipids and play multiple functions in plant growth and development. The three families of PLAs are: PLA1, PLA2 (sPLA), and patatin-related PLA (pPLA). The diverse functions that pPLAs play in the growth and development of a broad range of plants have been demonstrated by prior studies.
View Article and Find Full Text PDFStructural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenes.
Nat Commun
October 2023
Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia.
Listeriosis is one of the most serious foodborne diseases caused by the intracellular bacterium Listeria monocytogenes. Its two major virulence factors, broad-range phospholipase C (LmPC-PLC) and the pore-forming toxin listeriolysin O (LLO), enable the bacterium to spread in the host by destroying cell membranes. Here, we determine the crystal structure of LmPC-PLC and complement it with the functional analysis of this enzyme.
View Article and Find Full Text PDF4-Amino-TEMPO loaded liposomes as sensitive EPR and OMRI probes for the detection of phospholipase A2 activity.
Sci Rep
August 2023
Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126, Turin, Italy.
This work aims at developing a diagnostic method based on Electron Paramagnetic Resonance (EPR) measurements of stable nitroxide radicals released from "EPR silent" liposomes. The liposome destabilisation and consequent radical release is enzymatically triggered by the action of phospholipase A2 (PLA2) present in the biological sample of interest. PLA2 are involved in a broad range of processes, and changes in their activity may be considered as a unique valuable biomarker for early diagnoses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!