Synthetic Rewiring of Virus-like Particles via Circular Permutation Enables Modular Peptide Display and Protein Encapsulation
Year: 2025
Type: article
Abstract: Virus-like particles (VLPs) are self-assembling nanoparticles derived from viruses with potential as scaffolds for myriad applications. They are also excellent testbeds for engineering protein superstructures. Engineers often employ techniques such as amino acid substitutions and insertions/deletions. Yet evolution also utilizes circular permutation, a powerful natural strategy that has not been fully explored in engineering self-assembling protein nanoparticles. Here, we demonstrate this technique using the MS2 VLP as a model self-assembling, proteinaceous nanoparticle. We constructed, for the first time, a comprehensive circular permutation library of the fused MS2 coat protein dimer construct. The strategy revealed new terminal locations, validated via cryo-electron microscopy, that enabled C-terminal peptide tagging and led to a stable protein encapsulation strategy via covalent bonding - a feature the native coat protein does not permit. Our systematic study demonstrates the power of circular permutation for engineering new features as well as quantitatively and systematically exploring VLP structural determinants.
Source: ACS Nano
Institution: Northwestern University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Collaborative Research: Engineering MS2 Capsid Assembly Using Systematic Fitness Landscapes, ENGINEERING BACTERIAL MICROCOMPARTMENTS IN CLOSTRIDIUM AUTOETHANOGENUM TO OVERCOME BOTTLENECKS IN
SUSTAINABLE
PRODUCTION OF SYNTHETIC RUBBER, G9000159235, Chemistry of Life Processes Predoctoral Training Program, The Robert H. Lurie Comprehensive Cancer Center, Molecular Biophysics Training Program at Northwestern University
OpenAlex ID: W4415659235