20.500.12556/RUL-164449 Structural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenes 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$^{2+}$-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. hydrolases pathogens X-ray crystallography biokemija listerioza virulentnost bakterije true false true Angleški jezik Slovenski jezik Članek v reviji 2024-10-25 11:38:13 2024-10-25 11:38:14 2024-11-22 14:54:23 0000-00-00 00:00:00 2023 0 0 17 str. art. 6474 Vol. 14 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 577 2041-1723 10.1038/s41467-023-42134-4 170720003 RAZ_Petrisic_Nejc_2023.pdf RAZ_Petrisic_Nejc_2023.pdf 1 67CE68830134B0117362FAC2BCD2103E 54fcea9129863d21bee6faf4893425c9ca2842ac5b57136e6286bc408198c05c 8f6ae1f1-92b4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=194856 https://www.nature.com/articles/s41467-023-42134-4 0 ae786fac-92b4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=194857 Biotehniška fakulteta 0 0 0