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Accelerated evolution of a minimal 63-amino acid dual transcription factor
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Broedel, A., Rodrigues, R., Jaramillo, Alfonso and Isalan, M. (2020) Accelerated evolution of a minimal 63-amino acid dual transcription factor. Science Advances, 6 (24). eaba2728. doi:10.1126/sciadv.aba2728
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Official URL: http://dx.doi.org/10.1126/sciadv.aba2728
Abstract
Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previous efforts to engineer a minimal activator from λ Cro resulted in no activity in vivo in cells. In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as λ cI in vivo. To achieve this, we develop phagemid-assisted continuous evolution (PACEmid). We find that a peptide as small as 63 amino acids functions efficiently as an activator and/or repressor. To our knowledge, this is the smallest protein activator that enables polymerase recruitment, highlighting the capacity of transcription factors to evolve from very short peptide sequences.
| Item Type: | Journal Article | ||||||||||||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Transcription factors, Bacteriophages -- Genetics, Amino acids, Genetic transcription | ||||||||||||||||||||||||
| Journal or Publication Title: | Science Advances | ||||||||||||||||||||||||
| Publisher: | American Association for the Advancement of Science | ||||||||||||||||||||||||
| ISSN: | 2375-2548 | ||||||||||||||||||||||||
| Official Date: | 10 June 2020 | ||||||||||||||||||||||||
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| Volume: | 6 | ||||||||||||||||||||||||
| Number: | 24 | ||||||||||||||||||||||||
| Article Number: | eaba2728 | ||||||||||||||||||||||||
| DOI: | 10.1126/sciadv.aba2728 | ||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||
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