10.1021/acssynbio.8b00471.s001
Sophia Hasenjäger
Sophia
Hasenjäger
Jonathan Trauth
Jonathan
Trauth
Sebastian Hepp
Sebastian
Hepp
Juri Goenrich
Juri
Goenrich
Lars-Oliver Essen
Lars-Oliver
Essen
Christof Taxis
Christof
Taxis
Optogenetic Downregulation of Protein Levels with
an Ultrasensitive Switch
American Chemical Society
2019
module
Ultrasensitive Switch Optogenetic control
optogenetic multistep control
light-sensitive transcription factor
regulation
protein depletion kinetics
doxycycline-dependent transcriptional control
protein abundance
target protein
2019-04-08 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Optogenetic_Downregulation_of_Protein_Levels_with_an_Ultrasensitive_Switch/7998890
Optogenetic control of protein activity
is a versatile technique
to gain control over cellular processes, for example, for biomedical
and biotechnological applications. Among other techniques, the regulation
of protein abundance by controlling either transcription or protein
stability found common use as this controls the activity of any type
of target protein. Here, we report modules of an improved variant
of the photosensitive degron module and a light-sensitive transcription
factor, which we compared to doxycycline-dependent transcriptional
control. Given their modularity the combined control of synthesis
and stability of a given target protein resulted in the synergistic
down regulation of its abundance by light. This combined module exhibits
very high switching ratios, profound downregulation of protein abundance
at low light-fluxes, and fast protein depletion kinetics. Overall,
this synergistic optogenetic multistep control (SOMCo) module is easy
to implement and results in a regulation of protein abundance superior
to each individual component.