5F8K

Crystal structure of the Bac7(1-16) antimicrobial peptide bound to the Thermus thermophilus 70S ribosome

これはPDB形式変換不可エントリーです。

5F8K の概要

• エントリーDOI: 10.2210/pdb5f8k/pdb
• 分子名称: 23S ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• 機能のキーワード: ribosome, bacterial ribosome, proline-rich antimicrobial peptide, antibiotics, protein biosynthesis
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Secreted: P19661
• タンパク質・核酸の鎖数: 110
• 化学式量合計: 4404660.24

構造登録者

Seefeldt, A.C.,Graf, M.,Perebaskine, N.,Nguyen, F.,Arenz, S.,Mardirossian, M.,Scocchi, M.,Wilson, D.N.,Innis, C.A. (登録日: 2015-12-09, 公開日: 2016-02-03, 最終更新日: 2024-04-24)

主引用文献

Seefeldt, A.C.,Graf, M.,Perebaskine, N.,Nguyen, F.,Arenz, S.,Mardirossian, M.,Scocchi, M.,Wilson, D.N.,Innis, C.A.
Structure of the mammalian antimicrobial peptide Bac7(1-16) bound within the exit tunnel of a bacterial ribosome.
Nucleic Acids Res., 44:2429-2438, 2016

PubMed Abstract: Proline-rich antimicrobial peptides (PrAMPs) produced as part of the innate immune response of animals, insects and plants represent a vast, untapped resource for the treatment of multidrug-resistant bacterial infections. PrAMPs such as oncocin or bactenecin-7 (Bac7) interact with the bacterial ribosome to inhibit translation, but their supposed specificity as inhibitors of bacterial rather than mammalian protein synthesis remains unclear, despite being key to developing drugs with low toxicity. Here, we present crystal structures of the Thermus thermophilus 70S ribosome in complex with the first 16 residues of mammalian Bac7, as well as the insect-derived PrAMPs metalnikowin I and pyrrhocoricin. The structures reveal that the mammalian Bac7 interacts with a similar region of the ribosome as insect-derived PrAMPs. Consistently, Bac7 and the oncocin derivative Onc112 compete effectively with antibiotics, such as erythromycin, which target the ribosomal exit tunnel. Moreover, we demonstrate that Bac7 allows initiation complex formation but prevents entry into the elongation phase of translation, and show that it inhibits translation on both mammalian and bacterial ribosomes, explaining why this peptide needs to be stored as an inactive pro-peptide. These findings highlight the need to consider the specificity of PrAMP derivatives for the bacterial ribosome in future drug development efforts.

PubMed: 26792896
DOI: 10.1093/nar/gkv1545

実験手法

X-RAY DIFFRACTION (2.8 Å)