9D7T

Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with Api137 antimicrobial peptide, mRNA, A-site release factor 1, and deacylated P-site and E-site tRNAphe at 2.70A resolution

This is a non-PDB format compatible entry.

Summary for 9D7T

• Entry DOI: 10.2210/pdb9d7t/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• Functional Keywords: apidaecin; pramp; antibiotic; ribosome; translation; x-ray structure, ribosome
• Biological source: Thermus thermophilus HB8; More
• Total number of polymer chains: 114
• Total formula weight: 4586939.03

Authors

Aleksandrova, E.V.,Huang, W.,Baliga, C.,Atkinson, G.C.,Vazquez-Laslop, N.,Mankin, A.S.,Polikanov, Y.S. (deposition date: 2024-08-17, release date: 2024-11-13, Last modification date: 2025-03-19)

Primary citation

Huang, W.,Baliga, C.,Aleksandrova, E.V.,Atkinson, G.,Polikanov, Y.S.,Vazquez-Laslop, N.,Mankin, A.S.
Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects.
Embo Rep., 25:5194-5211, 2024

PubMed Abstract: 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.

PubMed: 39415050
DOI: 10.1038/s44319-024-00277-5

Experimental method

X-RAY DIFFRACTION (2.7 Å)