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.
journal_name
Sci Advjournal_title
Science advancesauthors
Brödel AK,Rodrigues R,Jaramillo A,Isalan Mdoi
10.1126/sciadv.aba2728subject
Has Abstractpub_date
2020-06-10 00:00:00pages
eaba2728issue
24issn
2375-2548pii
aba2728journal_volume
6pub_type
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