Structural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenesPetrišič, Nejc (Avtor) Adamek, Maksimiljan (Avtor) Kežar, Andreja (Avtor) Hočevar, Samo B. (Avtor) Žagar, Ema (Avtor) Anderluh, Gregor (Avtor) Podobnik, Marjetka (Avtor) hydrolasespathogensX-ray crystallographyListeriosis 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$^{2+}$-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.20232024-10-25 11:38:13Članek v reviji164449UDK: 577ISSN pri članku: 2041-1723DOI: 10.1038/s41467-023-42134-4COBISS_ID: 170720003sl