Year: 2024
Type: article
Abstract: Fusion of intrinsically disordered and globular proteins is a powerful strategy to create functional nanomaterials. However, the immutable nature of genetic encoding restricts the dynamic adaptability of nanostructures postexpression. To address this, we envisioned using a myristoyl switch, a protein that combines allostery and post-translational modifications─two strategies that modify protein properties without altering their sequence─to regulate intrinsically disordered protein (IDP)-driven nanoassembly. A typical myristoyl switch, allosterically activated by a stimulus, reveals a sequestered lipid for membrane association. We hypothesize that this conditional exposure of lipids can regulate the assembly of fusion proteins, a concept we term "liposwitching". We tested this by fusing recoverin, a calcium-dependent myristoyl switch, with elastin-like polypeptide, a thermoresponsive model IDP. Biophysical analyses confirmed recoverin's myristoyl-switch functionality, while dynamic light scattering and cryo-transmission electron microscopy showed distinct calcium- and lipidation-dependent phase separation and assembly. This study highlights liposwitching as a viable strategy for controlling DP-driven nanoassembly, enabling applications in synthetic biology and cellular engineering.
Source: Biomacromolecules
Institution: Syracuse University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1205195086, G1321126357, Zeiss LSM 980 with Airyscan2 microscope and Fast Mode for live cell and enhanced resolution imaging, CAREER: Post-translationally Lipidated Biopolymers As Multiphasic All-Aqueous Emulsions, G2415270547, G2929996310, An Integrated Computational and Experimental Approach to Reveal Design Principles for Responsive Nanomaterials from Lipidated Disordered Proteins, G3267397913, G3440716990, G3529059589, Cornell Center for Materials Research - MRSEC, G5917061246, G6351810044, MRI: Acquisition of a Liquid Chromatograph-High Resolution Mass Spectrometer to Characterize Organic Molecules of Environmental and Health Significance, G6538132396, G6671297155, G7195225199, G7767248047, Genetically Encoded Lipidation to Manipulate Structure, Assembly, and Phase Behavior of Proteins
OpenAlex ID: W4404040097