Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects
Huang, Weiping ; Baliga, Chetana ; Aleksandrova, Elena V. ; Atkinson, Gemma LU
; Polikanov, Yury S.
; Vázquez-Laslop, Nora
and Mankin, Alexander S.
(2024)
In EMBO Reports
25(11).
p.5194-5211
- 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... (More)
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.
(Less)
- author
- Huang, Weiping
; Baliga, Chetana
; Aleksandrova, Elena V.
; Atkinson, Gemma
LU
; Polikanov, Yury S.
; Vázquez-Laslop, Nora
and Mankin, Alexander S.
- organization
- publishing date
- 2024-11-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antibiotics, PrAMP, Ribosome, Structure, Translation
- in
- EMBO Reports
- volume
- 25
- issue
- 11
- pages
- 18 pages
- publisher
- Springer Science and Business Media B.V.
- external identifiers
-
- scopus:85207281249
- pmid:39415050
- ISSN
- 1469-221X
- DOI
- 10.1038/s44319-024-00277-5
- language
- English
- LU publication?
- yes
- id
- eb18bf88-7082-4bc5-a636-899398bdc27c
- date added to LUP
- 2025-01-02 15:18:48
- date last changed
- 2025-06-06 04:17:41
@article{eb18bf88-7082-4bc5-a636-899398bdc27c,
abstract = {{<p>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.</p>}},
author = {{Huang, Weiping and Baliga, Chetana and Aleksandrova, Elena V. and Atkinson, Gemma and Polikanov, Yury S. and Vázquez-Laslop, Nora and Mankin, Alexander S.}},
issn = {{1469-221X}},
keywords = {{Antibiotics; PrAMP; Ribosome; Structure; Translation}},
language = {{eng}},
month = {{11}},
number = {{11}},
pages = {{5194--5211}},
publisher = {{Springer Science and Business Media B.V.}},
series = {{EMBO Reports}},
title = {{Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects}},
url = {{http://dx.doi.org/10.1038/s44319-024-00277-5}},
doi = {{10.1038/s44319-024-00277-5}},
volume = {{25}},
year = {{2024}},
}