Selection of protein-protein interactions of desired affinities with a bandpass circuit
- We have developed a genetic circuit in Escherichia coli that can be used to select for protein-protein interactions of different strengths by changing antibiotic concentrations in the media. The genetic circuit links protein-protein interaction strength to beta-lactamase activity while simultaneously imposing tuneable positive and negative selection pressure for beta-lactamase activity. Cells only survive if they express interacting proteins with affinities that fall within set high- and low-pass thresholds; i.e. the circuit therefore acts as a bandpass filter for protein-protein interactions. We show that the circuit can be used to recover protein-protein interactions of desired affinity from a mixed population with a range of affinities. The circuit can also be used to select for inhibitors of protein-protein interactions of defined strength. (C) 2018 Elsevier Ltd. All rights reserved.
Author details: | Katherine Emily BrechunORCiD, Katja Maren ArndtORCiDGND, G. Andrew WoolleyORCiD |
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DOI: | https://doi.org/10.1016/j.jmb.2018.11.011 |
ISSN: | 0022-2836 |
ISSN: | 1089-8638 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30448232 |
Title of parent work (English): | Journal of molecular biology : JMB |
Publisher: | Elsevier |
Place of publishing: | London |
Publication type: | Article |
Language: | English |
Date of first publication: | 2018/11/15 |
Publication year: | 2018 |
Release date: | 2021/04/20 |
Tag: | biological engineering; genetic circuit; protein-protein interactions; selection system; synthetic biology; twin-arginine translocation |
Volume: | 431 |
Issue: | 2 |
Number of pages: | 10 |
First page: | 391 |
Last Page: | 400 |
Funding institution: | National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R33MH105724]; Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of Canada; German Academic Exchange Service (DAAD) Deutscher Akademischer AustauschdienstDeutscher Akademischer Austausch Dienst (DAAD) |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer review: | Referiert |
Publishing method: | Open Access / Green Open-Access |