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Updated: Dec 25, 2025
09:40
Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
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Structure and Function of the Bacterial Protein Toxin Phenomycin.
Bente K Hansen1, Camilla K Larsen2, Jakob T Nielsen1
1Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
Structure (London, England : 1993)
|March 30, 2020
Summary
Phenomycin, a bacterial protein, directly inhibits mammalian cell translation. Its toxicity is limited by endosomal escape, and a specific peptide loop is crucial for its activity.
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- Phenomycin is an 89-amino acid bacterial mini-protein with nanomolar toxicity to mammalian cells.
- It inhibits eukaryotic ribosome function, targeting translation initiation in cell-free systems.
- Fundamental questions about phenomycin's cellular activity remain unanswered.
Purpose of the Study:
- To elucidate the cellular activity and toxicity mechanisms of phenomycin.
- To investigate the cellular uptake and identify the rate-limiting step for toxicity.
- To determine the structure of phenomycin and identify key toxic determinants.
Main Methods:
- Morphological profiling to assess cellular effects.
- Cellular uptake studies and endosomal escape assays.
- Solution-phase NMR spectroscopy for structural determination.
- Bioinformatic and functional comparisons with homologs.
Main Results:
- Phenomycin directly inhibits translation, underlying its cellular toxicity.
- Endosomal escape is the rate-limiting step for phenomycin's cellular uptake and toxicity.
- A high-resolution NMR structure revealed phenomycin's fold.
- A critical toxic peptide segment within a structural loop was identified.
Conclusions:
- Phenomycin exerts toxicity by directly inhibiting translation in mammalian cells.
- Understanding phenomycin's uptake and structure provides insights into its mechanism of action.
- A specific peptide loop is essential for phenomycin's toxicity, offering potential targets for future research.
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