The structure of the Vibrio natriegens 70S ribosome in complex with the proline-rich antimicrobial peptide Bac5(1-17)
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Updated: May 12, 2025
Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
Published on: August 11, 2018
Karoline Raulf1, Timm O Koller1, Bertrand Beckert1
1Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg 20146, Germany.
Abstract:
Proline-rich antimicrobial peptides (PrAMPs) are produced as part of the innate immune response of animals, insects, and plants. The well-characterized mammalian PrAMP bactenecin-5 (Bac5) has been shown to help fight bacterial infection by binding to the bacterial ribosome and inhibiting protein synthesis. In the absence of Bac5-ribosome structures, the binding mode of Bac5 and exact mechanism of action has remained unclear. Here, we present a cryo-electron microscopy structure of Bac5 in complex with the 70S ribosome from the Gram-negative marine bacterium Vibrio natriegens. The structure shows that, despite sequence similarity to Bac7 and other type I PrAMPs, Bac5 displays a completely distinct mode of interaction with the ribosomal exit tunnel. Bac5 overlaps with the binding site of both A- and P-site transfer RNAs bound at the peptidyltransferase center, suggesting that this type I PrAMP can interfere with late stages of translation initiation as well as early stages of elongation. Collectively, our study presents a ribosome structure from V. natriegens, a fast-growing bacterium that has interesting biotechnological and synthetic biology applications, as well as providing additional insights into the diverse binding modes that type I PrAMPs can utilize to inhibit protein synthesis.
Insights
Bactenecin-5 (Bac5), an antimicrobial peptide, inhibits bacterial protein synthesis by binding to the ribosome. A new cryo-EM structure reveals Bac5
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Proline-rich antimicrobial peptides (PrAMPs) are key components of innate immunity across diverse organisms.
- Bactenecin-5 (Bac5), a mammalian PrAMP, targets bacterial ribosomes to inhibit protein synthesis, but its precise binding and mechanism were unknown.
Purpose of the Study:
- To elucidate the structural basis of Bac5-ribosome interaction.
- To understand the mechanism by which Bac5 inhibits bacterial protein synthesis.
- To characterize the 70S ribosome structure of Vibrio natriegens.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure of Bac5 bound to the 70S ribosome.
- High-resolution structural analysis was performed on the Bac5-ribosome complex.
Main Results:
- A distinct binding mode of Bac5 within the ribosomal exit tunnel was identified, differing from other type I PrAMPs.
- Bac5 was observed to occupy the binding sites of A- and P-site transfer RNAs at the peptidyltransferase center.
- The structure provides insights into Bac5's inhibition of both translation initiation and elongation.
Conclusions:
- Bac5 employs a unique ribosomal interaction mechanism to inhibit protein synthesis.
- The study reveals the 70S ribosome structure of Vibrio natriegens, a bacterium with biotechnological relevance.
- Findings expand the understanding of diverse PrAMP binding modes and their antimicrobial functions.
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