Crystal structure of the metaeffector MesI (Lpg2505) from Legionella pneumophila
Dominik A Machtens1, Jonas M Willerding1, Susanne Eschenburg1
1Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Abstract:
Persistence and replication of the gram-negative bacterium Legionella pneumophila in the human host cell depend on so-called effector proteins that target diverse cellular functions and modulate them in favor of the pathogen. We solved the crystal structure of the L. pneumophila effector protein MesI de novo to a resolution of 2.2 Å. The 34 kDa polypeptide chain folds into two distinct α-helical domains. The larger C-terminal domain shows similarity to tetratricopeptide repeat proteins. Using size-exclusion chromatography, we confirmed that MesI binds tightly to full-length SidI and that deletion of either the N- or the C-terminus weakens the interaction. Based on the three-dimensional structure of MesI we suggest a possible binding mode for SidI and identified two homologs of MesI within the proteome of L. pneumophila that do not bind to SidI, but may act as specific inhibitors of other yet to be identified effectors.
Insights
Legionella pneumophila uses effector proteins like MesI to infect human cells. Researchers determined the MesI protein structure, revealing how it interacts with SidI and potentially other effectors.
Area of Science:
- Microbiology
- Structural Biology
- Molecular Biology
Background:
- Legionella pneumophila utilizes effector proteins to manipulate host cells for replication.
- Understanding these effector proteins is crucial for combating bacterial infections.
Purpose of the Study:
- To determine the de novo crystal structure of the Legionella pneumophila effector protein MesI.
- To investigate the interaction between MesI and the effector protein SidI.
Main Methods:
- X-ray crystallography was used to solve the MesI structure to 2.2 Å resolution.
- Size-exclusion chromatography confirmed the binding affinity between MesI and SidI.
Main Results:
- The MesI protein (34 kDa) comprises two distinct α-helical domains, with the C-terminal domain resembling tetratricopeptide repeat proteins.
- MesI binds tightly to full-length SidI, with N- or C-terminal deletions weakening this interaction.
- Two MesI homologs in Legionella pneumophila were identified that do not bind SidI, suggesting alternative functions.
Conclusions:
- The determined structure of MesI provides insights into its binding mechanism with SidI.
- MesI homologs may function as specific inhibitors of other Legionella effector proteins, offering new avenues for research.
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