Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 21, Pages 5432-5437Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1800527115
Keywords
synthetic biology; directed evolution; protein cage; nucleocapsid
Categories
Funding
- ETH Zurich
- European Research Council (ERC) Advanced Grant [ERC-AdG-2012-321295]
- Human Frontier Science Program Long-Term Fellowship [LT000426/2015-L]
- Uehara Memorial Foundation Research Fellowship
- ETH Zurich Postdoctoral Fellowship - Marie Curie Actions Program
Ask authors/readers for more resources
Viruses are remarkable nanomachines that efficiently hijack cellular functions to replicate and self-assemble their components within a complex biological environment. As all steps of the viral life cycle depend on formation of a protective proteinaceous shell that packages the DNA or RNA genome, bottom-up construction of virus-like nucleocapsids from nonviral materials could provide valuable insights into virion assembly and evolution. Such constructs could also serve as safe alternatives to natural viruses for diverse nano-and biotechnological applications. Here we show that artificial virus-like nucleocapsids can be generated-rapidly and surprisingly easily-by engineering and laboratory evolution of a nonviral protein cage formed by Aquifex aeolicus lumazine synthase (AaLS) and its encoding mRNA. Cationic peptides were appended to the engineered capsid proteins to enable specific recognition of packaging signals on cognate mRNAs, and subsequent evolutionary optimization afforded nucleocapsids with expanded spherical structures that encapsulate their own full-length RNA genome in vivo and protect the cargo molecules from nucleases. These findings provide strong experimental support for the hypothesis that subcellular protein-bounded compartments may have facilitated the emergence of ancient viruses.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available