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| Status |
Public on Jun 18, 2024 |
| Title |
Sequence diversity of apidaecin-like peptides arresting the terminating ribosome |
| Organism |
Escherichia coli |
| Experiment type |
Other
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| Summary |
The Proline-rich Antimicrobial Peptide (PrAMP) apidaecin (Api) inhibits translation by binding in the ribosomal nascent peptide exit tunnel, trapping release factors RF1 or RF2, and arresting ribosomes at stop codons. To explore the extent of sequence variations of the native 18-amino acid Api that allows it to preserve its activity, we screened a library of synthetic mutant Api genes expressed in bacterial cells, resulting in nearly 350,000 peptide variants with multiple substitutions. By applying orthogonal negative and positive selection strategies, we identified a number of multi-substituted Api variants capable of arresting ribosomes at stop codons. Our findings underscore the critical contribution of specific amino acid residues of the peptide for its on-target function while significantly expanding the variety of PrAMPs acting on the terminating ribosome. Additionally, some of the tested synthesized multi-substituted Api variants exhibit improved antibacterial activity compared to that of the wild type PrAMP and may constitute the starting point to develop clinically useful antimicrobials.
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| Overall design |
We used deep mutational analysis combined with orthogonal selection strategies to identify multi-substituted variants of the antibacterial peptide apidaecin (Api) that preserve the ability of binding to the ribosome and inhibit translation termination.
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| Contributor(s) |
Huang W, Baliga C, Mankin AS, Vázquez-Laslop N |
| Citation(s) |
38953159 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI162961 |
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action |
BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS |
Alexander S Mankin |
| R01 AI162961 |
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action |
BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS |
Nora Vazquez-Laslop |
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| Submission date |
Jun 14, 2024 |
| Last update date |
Sep 17, 2024 |
| Contact name |
Alexander Mankin |
| E-mail(s) |
shura@uic.edu
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| Organization name |
University of Illinois at Chicago
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| Department |
College of Pharmacy
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| Lab |
Mankin/Vázquez-Laslop lab
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| Street address |
900 S. Ashland Ave, Rm. 3052,
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| City |
Chicago |
| State/province |
Illinois |
| ZIP/Postal code |
60612 |
| Country |
USA |
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| Platforms (1) |
| GPL16085 |
Illumina MiSeq (Escherichia coli) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA1124079 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE269894_NS_aa_table_filtered_raw_counts.txt.gz |
677.6 Mb |
(ftp)(http) |
TXT |
| GSE269894_PS_AA_counts.xlsx |
30.7 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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