Genetically Engineered\nLiposwitch-Based Nanomaterials

Fusion of intrinsically disordered and globular proteins\nis a powerful\nstrategy to create functional nanomaterials. However, the immutable\nnature of genetic encoding restricts the dynamic adaptability of nanostructures\npostexpression. To address this, we envisioned using a myristoyl switch,\na protein that combines allostery and post-translational modificationstwo\nstrategies that modify protein properties without altering their sequenceto\nregulate intrinsically disordered protein (IDP)-driven nanoassembly.\nA typical myristoyl switch, allosterically activated by a stimulus,\nreveals a sequestered lipid for membrane association. We hypothesize\nthat this conditional exposure of lipids can regulate the assembly\nof fusion proteins, a concept we term “liposwitching”.\nWe tested this by fusing recoverin, a calcium-dependent myristoyl\nswitch, with elastin-like polypeptide, a thermoresponsive model IDP.\nBiophysical analyses confirmed recoverin’s myristoyl-switch\nfunctionality, while dynamic light scattering and cryo-transmission\nelectron microscopy showed distinct calcium- and lipidation-dependent\nphase separation and assembly. This study highlights liposwitching\nas a viable strategy for controlling DP-driven nanoassembly, enabling\napplications in synthetic biology and cellular engineering.