NAD(H)-mediated tetramerization controls the activity of Legionella pneumophila phospholipase PlaB

• DOI: 10.1073/pnas.2017046118
• Publication Date: 2021-06-01T22:20:52Z
• Authors: Maurice Diwo; Wiebke Michel; Philipp Aurass; Katja Kuhle-Keindorf; Jan Pippel; Joern Krausze; Sabrina Wamp; Christina Lang; Wulf Blankenfeldt; Antje Flieger
• Keywords: Bacterial Proteins; Phospholipases; Protein Conformation, beta-Strand; Protein Multimerization; Crystallography, X-Ray; NAD; Protein Structure, Quaternary; info:eu-repo/classification/ddc/500; Legionella pneumophila

Significance

Secreted bacterial phospholipases, which hydrolyze host membranes, may also harm the pathogen itself. Sophisticated activation mechanisms are therefore required to prevent self-damage before protein export but warrant activity at the pathogen–host interface. Here we structurally analyzed PlaB, a surface-exposed highly active phospholipase and virulence factor of the lung pathogen Legionella pneumophila . Unexpectedly, we found that NAD(H), a central cofactor of energy metabolism, stabilizes an inactive tetrameric form of PlaB. Since NAD(H) is confined to the intracellular milieu of the bacterium, we propose that this sophisticated NAD(H)-dependent oligomerization mechanism protects L. pneumophila from damage and simultaneously enables the function of PlaB as a virulence factor after export and association to the bacterial surface.