sb8b00471_si_001.pdf (3.26 MB)
Optogenetic Downregulation of Protein Levels with an Ultrasensitive Switch
journal contribution
posted on 2019-04-08, 00:00 authored by Sophia Hasenjäger, Jonathan Trauth, Sebastian Hepp, Juri Goenrich, Lars-Oliver Essen, Christof TaxisOptogenetic 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.