Short proline-rich antimicrobial peptides (PrAMPs) are a promising class of antibiotics that use novel mechanisms, thus offering the potential to overcome the health threat of multiresistant pathogens. The peptides bind to the bacterial 70S ribosome and can inhibit protein translation. We report that PrAMPs can be divided into two classes, with each class binding to a different site, and thus use different lethal mechanisms. Oncocin-type peptides inhibit protein translation in Escherichia coli by binding to the exit tunnel of the 70S ribosome with half maximal inhibitory concentrations (IC50 values) of around 2 to 6 μmol L(-1), whereas apidaecin-type peptides block the assembly of the large (50S) subunit of the ribosome, resulting in similar IC50 values. The revealed mechanisms should allow the design of new antibiotics to overcome current bacterial resistance mechanisms.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cbic.201500375 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rapid structural analysis of bacterial ribosomes in situ.
Commun Biol
January 2025
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) and associated data processing software packages. In contrast, analogous structural analysis in cells via cryo-electron tomography (cryo-ET) remains challenging due to critical technical bottlenecks, including low-throughput sample preparation and imaging, and laborious data processing methods. Here, we describe a rapid in situ cryo-ET sample preparation and data analysis workflow that results in the routine determination of sub-nm resolution ribosomal structures.
View Article and Find Full Text PDFMolecular and structural basis of a subfamily of PrfH rescuing both the damaged and intact ribosomes stalled in translation.
bioRxiv
January 2025
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
In bacteria, spontaneous mRNAs degradation and ribotoxin-induced RNA damage are two main biological events that lead to the stall of protein translation. The ubiquitous trans-translation system as well as several alternative rescue factors (Arfs) are responsible for rescuing the stalled ribosomes caused by truncated mRNAs that lack the stop codons. To date, protein release factor homolog (PrfH) is the only factor known to rescue the stalled ribosome damaged by ribotoxins.
View Article and Find Full Text PDFNovel archaeal ribosome dimerization factor facilitating unique 30S-30S dimerization.
Nucleic Acids Res
January 2025
Central European Institute of Technology, Masaryk University, Kamenice 5, Brno 625 00, Czech Republic.
Protein synthesis (translation) consumes a substantial proportion of cellular resources, prompting specialized mechanisms to reduce translation under adverse conditions. Ribosome inactivation often involves ribosome-interacting proteins. In both bacteria and eukaryotes, various ribosome-interacting proteins facilitate ribosome dimerization or hibernation, and/or prevent ribosomal subunits from associating, enabling the organisms to adapt to stress.
View Article and Find Full Text PDFProline-Rich Antimicrobial Peptides from Invertebrates.
Molecules
December 2024
Department of Immunobiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19 St., 20-033 Lublin, Poland.
Antimicrobial peptides (AMPs) constitute a large and diverse group of molecules with antibacterial, antifungal, antiviral, antiprotozoan, and anticancer activity. In animals, they are key components of innate immunity involved in fighting against various pathogens. Proline-rich (Pr) AMPs are characterized by a high content of proline (and arginine) residues that can be organized into Pro-Arg-Pro motifs.
View Article and Find Full Text PDFProkaryotic ABCF proteins in overcoming ribosomal stalling: mechanisms, evolution, and perspective for applications in Bio-manufacturing.
Biosci Biotechnol Biochem
December 2024
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu-shi, Toyama, Japan.
ABCF proteins (ABCFs) are key components of prokaryotic translation systems, resolving ribosomal stalling. These ATPases contain two ATPase domains and interdomain linker, the length and composition of which are key determinants of their function. Antibiotic resistance ABCF (ARE-ABCFs) proteins, counteract ribosome-targeting antibiotics by binding to the E site of the 70S ribosome, promoting drug dissociation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!