Please use this identifier to cite or link to this item:
doi:10.22028/D291-35225
Title: | Generation of Lasso Peptide-Based ClpP Binders |
Author(s): | Malik, Imran T. Hegemann, Julian D. Brötz-Oesterhelt, Heike |
Language: | English |
Title: | International Journal of Molecular Sciences |
Volume: | 23 (2022) |
Issue: | 1 |
Publisher/Platform: | MDPI |
Year of Publication: | 2021 |
Free key words: | Clp protease Clp ATPase lasso peptide epitope grafting mutagenesis bioengineering acyldepsipeptide ADEP natural product proteolysis |
DDC notations: | 500 Science |
Publikation type: | Journal Article |
Abstract: | The Clp protease system fulfills a plethora of important functions in bacteria. It consists of a tetradecameric ClpP barrel holding the proteolytic centers and two hexameric Clp-ATPase rings, which recognize, unfold, and then feed substrate proteins into the ClpP barrel for proteolytic degradation. Flexible loops carrying conserved tripeptide motifs protrude from the Clp-ATPases and bind into hydrophobic pockets (H-pockets) on ClpP. Here, we set out to engineer microcin J25 (MccJ25), a ribosomally synthesized and post-translationally modified peptide (RiPP) of the lasso peptide subfamily, by introducing the conserved tripeptide motifs into the lasso peptide loop region to mimic the Clp-ATPase loops. We studied the capacity of the resulting lasso peptide variants to bind to ClpP and affect its activity. From the nine variants generated, one in particular (12IGF) was able to activate ClpP from Staphylococcus aureus and Bacillus subtilis. While 12IGF conferred stability to ClpP tetradecamers and stimulated peptide degradation, it did not trigger unregulated protein degradation, in contrast to the H-pocket-binding acyldepsipeptide antibiotics (ADEPs). Interestingly, synergistic interactions between 12IGF and ADEP were observed. |
DOI of the first publication: | 10.3390/ijms23010465 |
URL of the first publication: | https://www.mdpi.com/1422-0067/23/1/465 |
Link to this record: | urn:nbn:de:bsz:291--ds-352250 hdl:20.500.11880/35326 http://dx.doi.org/10.22028/D291-35225 |
ISSN: | 1422-0067 |
Date of registration: | 28-Feb-2023 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/ijms23010465/s1 |
Faculty: | NT - Naturwissenschaftlich- Technische Fakultät |
Department: | NT - Pharmazie |
Professorship: | NT - Keiner Professur zugeordnet |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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ijms-23-00465-v2.pdf | 2,37 MB | Adobe PDF | View/Open |
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