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Systematic Engineering of Virus-Like Particles to Identify Self-Assembly Rules for Shifting Particle Size
Open accessPreprint — published as 10.1016/j.virol.2023.01.002 · Paper page
Abstract
Virus-like particles (VLPs) are promising scaffolds for biomaterials as well as diagnostic and therapeutic applications. However, there are some key challenges to be solved, such as the ability to engineer alternate sizes for varied use cases. To this end, we created a library of MS2 VLP variants at two key residues in the coat protein which have been implicated as important to controlling VLP size and geometry. By adapting a method for systematic mutagenesis coupled with size-based selections and high-throughput sequencing as a readout, we developed a quantitative assessment of two residues in MS2 coat protein that govern the size shift in MS2 VLPs. We then applied the strategy to the equivalent residues in Qβ VLPs, an MS2 homolog, and demonstrate that the analogous pair of residues are also able to impact VLP size and shape. These results underscore the power of fitness landscapes in identifying critical features for assembly.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Ikwuagwu, B., Hartman, E., Mills, C., & Tullman-Ercek, D.
- Affiliations
- Northwestern University (US)
- University of California, Berkeley (US)
- ORCID
- Mills, Carolyn
- Venue
- Virology
- Publisher
- openRxiv
- Published
- 2022-09-03
- Volume
- 579
- Pages
- 137-147
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC10776172
- OpenAlex
- W4313560633
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Virology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (2043973)
- U.S. Department of Defense (32 CFR 168 a)
- National Institutes of Health
- National Defense Science and Engineering Graduate (32 CFR 168a, CFR 168a)
- National Institute of General Medical Sciences (T32GM105538)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Air Force Office of Scientific Research
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Keywords
- virus-like particles, MS2 coat protein, self-assembly, fitness landscape, next-generation sequencing, protein engineering
- MeSH terms
- Particle Size, Gene Library, Vaccines, Virus-Like Particle
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