Chimeric protein switch for the optogenetic control of amyloidogenesis

Abstract

The present invention provides an optogenetic chimeric fusion polypeptide comprising an optimized amino acid sequence of the plant phototropin domain LOV2 fused to an amino acid sequence of the bacterial amyloidogenic effector RepA-WH1. Optimized LOV2 enables navigation through the folding landscape of RepA-WH1 from solubility to its aggregation as oligomers or amyloid fibres. Thus, this polypeptide assembles as hydrogels and amyloid fibres in the darkness, while under blue light illumination forms oligomeric particles that are proteotoxic for cells, preferably bacteria. This polypeptide is therefore proposed for inducing the formation of cytotoxic amyloid oligomers in cells that are targeted for killing.