| Autor: |
Huang, Weiping, Baliga, Chetana, Aleksandrova, Elena V, Atkinson, Gemma, Polikanov, Yury S, Vázquez-Laslop, Nora, Mankin, Alexander S |
| Zdroj: |
EMBO Reports; Nov2024, Vol. 25 Issue 11, p5194-5211, 18p |
| Abstrakt: |
Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough—all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs' C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence. Synopsis: This study identifies new Type II proline-rich antimicrobial peptides from insects that trap ribosomes at stop codons and presents the structure of one of the most active peptides in complex with the bacterial ribosome. Genome mining identified new apidaecin-like Type II proline-rich antimicrobial peptides encoded in insect genomes. These peptides target bacterial ribosomes trapping them at stop codons and inducing stop codon readthrough. The pharmacophore of a peptide from Frieseomelitta varia interacts with the ribosomal nascent peptide exit tunnel. This study identifies new ribosome-targeting Type II proline-rich antimicrobial peptides in insect genomes that trap the ribosome at stop codons and presents the structure of one of the most active peptides in complex with the bacterial ribosome. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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