8CQM

Broad-range phospholipase C from Listeria monocytogenes

Summary for 8CQM

• Entry DOI: 10.2210/pdb8cqm/pdb
• Descriptor: Phospholipase C, GLYCEROL, ZINC ION, ... (5 entities in total)
• Functional Keywords: zinc-binding, monomer, phospholipase, listeria, lipids, membrane, virulence factor, hydrolase
• Biological source: Listeria monocytogenes
• Total number of polymer chains: 2
• Total formula weight: 55906.46

Authors

Petrisic, N.,Podobnik, M. (deposition date: 2023-03-06, release date: 2023-10-18, Last modification date: 2023-10-25)

Primary citation

Petrisic, N.,Adamek, M.,Kezar, A.,Hocevar, S.B.,Zagar, E.,Anderluh, G.,Podobnik, M.
Structural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenes.
Nat Commun, 14:6474-6474, 2023

PubMed Abstract: 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.

PubMed: 37838694
DOI: 10.1038/s41467-023-42134-4

Experimental method

X-RAY DIFFRACTION (2 Å)