Structural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenes

Petrišič, Nejc (author), Adamek, Maksimiljan (author), Kežar, Andreja (author), Hočevar, Samo B. (author), Žagar, Ema (author), Anderluh, Gregor (author), Podobnik, Marjetka (author)

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.

• Language: English
• Keywords: hydrolases, pathogens, X-ray crystallography
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 17 str.
• Numbering: Vol. 14, art. 6474
• PID: 20.500.12556/RUL-164449
• UDC: 577
• ISSN on article: 2041-1723
• DOI: 10.1038/s41467-023-42134-4
• COBISS.SI-ID: 170720003
• Publication date in RUL: 25.10.2024

Record is a part of a journal

• Title: Nature communications
• Shortened title: Nat. commun.
• Publisher: Springer Nature
• ISSN: 2041-1723
• COBISS.SI-ID: 2315876

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: biokemija, listerioza, virulentnost, bakterije