EMD-19429

Single-particle
2.44 Å
EMD-19429 Deposition: 17/01/2024
Map released: 22/05/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-19429

Escherichia coli 50S subunit in complex with the antimicrobial peptide Api88 - conformation III

EMD-19429

Single-particle
2.44 Å
EMD-19429 Deposition: 17/01/2024
Map released: 22/05/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Escherichia coli, Apis mellifera
Sample: Api88 in complex with the large ribosomal subunit - conformation III
Fitted models: 8rq2

Deposition Authors: Lauer S, Nikolay R , Spahn C
Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88.
PUBMED: 38730238
DOI: doi:10.1038/s41467-024-48027-4
ISSN: 2041-1723
Abstract:
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis by binding to the polypeptide exit tunnel (PET) near the peptidyl transferase center. Api137, an optimized derivative of honeybee PrAMP apidaecin, inhibits protein expression by trapping release factors (RFs), which interact with stop codons on ribosomes to terminate translation. This study uses cryo-EM, functional assays and molecular dynamic (MD) simulations to show that Api137 additionally occupies a second binding site near the exit of the PET and can repress translation independently of RF-trapping. Api88, a C-terminally amidated (-CONH2) analog of Api137 (-COOH), binds to the same sites, occupies a third binding pocket and interferes with the translation process presumably without RF-trapping. In conclusion, apidaecin-derived PrAMPs inhibit bacterial ribosomes by multimodal mechanisms caused by minor structural changes and thus represent a promising pool for drug development efforts.