8RPZ

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

8RPZ の概要

• エントリーDOI: 10.2210/pdb8rpz/pdb
• EMDBエントリー: 19427
• 分子名称: Large ribosomal subunit protein bL32, Large ribosomal subunit protein uL3, Large ribosomal subunit protein uL4, ... (32 entities in total)
• 機能のキーワード: ribosome, antimicrobial peptide, rna, ribosomal protein, pramp, proline-rich peptide, antibiotics, 50s, api88
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 34
• 化学式量合計: 1351190.19

構造登録者

Lauer, S.,Nikolay, R.,Spahn, C. (登録日: 2024-01-17, 公開日: 2024-05-22, 最終更新日: 2024-10-16)

主引用文献

Lauer, S.M.,Reepmeyer, M.,Berendes, O.,Klepacki, D.,Gasse, J.,Gabrielli, S.,Grubmuller, H.,Bock, L.V.,Krizsan, A.,Nikolay, R.,Spahn, C.M.T.,Hoffmann, R.
Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88.
Nat Commun, 15:3945-3945, 2024

PubMed 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 (-CONH) 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.

PubMed: 38730238
DOI: 10.1038/s41467-024-48027-4

実験手法

ELECTRON MICROSCOPY (2.44 Å)