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Synthetic Rewiring of Virus-like Particles via Circular Permutation Enables Modular Peptide Display and Protein
Shiqi Liang1, Kaavya Butaney2, Daniel de Castro Assumpção2
1Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, Illinois 60208, United States.
ACS Nano
|October 29, 2025
Summary
Circular permutation engineering of virus-like particles (VLPs) enables novel applications. This study demonstrates its power for creating protein superstructures and exploring VLP design.
Area of Science:
- Biotechnology
- Structural Biology
- Nanotechnology
Background:
- Virus-like particles (VLPs) are self-assembling protein nanoparticles with broad applications.
- Protein engineering commonly uses substitutions and indels, but natural strategies like circular permutation are less explored.
- MS2 VLP serves as a model system for studying self-assembling protein nanoparticles.
Purpose of the Study:
- To explore circular permutation as a strategy for engineering self-assembling protein nanoparticles.
- To engineer novel features into the MS2 VLP using circular permutation.
- To systematically investigate VLP structural determinants through protein engineering.
Main Methods:
- Construction of a comprehensive circular permutation library for the MS2 coat protein dimer.
- Validation of engineered VLP structures using cryo-electron microscopy.
- Development of C-terminal peptide tagging and protein encapsulation strategies.
Main Results:
- Identification of terminal locations enabling C-terminal peptide tagging.
- Demonstration of a novel protein encapsulation strategy via covalent bonding.
- Quantitative and systematic exploration of VLP structural determinants.
Conclusions:
- Circular permutation is a powerful tool for engineering virus-like particles.
- This technique enables the creation of novel functionalities not present in native VLPs.
- The study provides a systematic framework for VLP structural and functional engineering.
Keywords:
cryo-electron microscopymolecular libraryprotein encapsulationself-assemblyvirus-like particlesMore Related Videos
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