Genetic evidence for a regulated cysteine protease catalytic triad in LegA7, a Legionella pneumophila protein that impinges on a stress response pathway.
Dar HershkovitzEmy J ChenAlexander W EnsmingerAisling S DuganKaleigh T ConwayAlex C JoyceGil SegalRalph R IsbergPublished in: mSphere (2024)
grows in a membrane-bound compartment in macrophages during disease. Construction of the compartment requires a dedicated secretion system that translocates virulence proteins into host cells. One of these proteins, LegA7, is shown to activate a stress response pathway in host cells called the mitogen-activated protein kinase (MAPK) pathway. The effects on the mammalian MAPK pathway were reconstructed in yeast, allowing the development of a strategy to identify the role of individual domains of LegA7. A domain similar to cysteine proteases is demonstrated to be critical for impinging on the MAPK pathway, and the catalytic activity of this domain is required for targeting this path. In addition, a conserved series of repeats, called ankyrin repeats, controls this activity. Data are provided that argue the interaction of the ankyrin repeats with unknown targets probably results in activation of the cysteine protease domain.
Keyphrases
- induced apoptosis
- signaling pathway
- oxidative stress
- cell cycle arrest
- pi k akt
- transcription factor
- escherichia coli
- staphylococcus aureus
- machine learning
- drug delivery
- living cells
- cell proliferation
- fluorescent probe
- cell death
- electronic health record
- dna methylation
- genome wide
- endoplasmic reticulum stress
- deep learning
- cancer therapy
- antimicrobial resistance
- biofilm formation
- amino acid
- protein kinase
- crystal structure