Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein.
Amino Acid Substitution
Aquifex
/ enzymology
Bacterial Proteins
/ chemistry
Capsid
/ chemistry
Cryoelectron Microscopy
Directed Molecular Evolution
Multienzyme Complexes
/ chemistry
Nucleocapsid
/ chemistry
Protein Domains
Protein Structure, Secondary
Protein Subunits
RNA, Messenger
/ chemistry
Ribonucleases
/ metabolism
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
11 06 2021
11 06 2021
Historique:
received:
22
12
2020
accepted:
29
04
2021
entrez:
11
6
2021
pubmed:
12
6
2021
medline:
22
6
2021
Statut:
ppublish
Résumé
Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.
Identifiants
pubmed: 34112695
pii: 372/6547/1220
doi: 10.1126/science.abg2822
pmc: PMC7612296
mid: EMS140864
doi:
Substances chimiques
Bacterial Proteins
0
Multienzyme Complexes
0
Protein Subunits
0
RNA, Messenger
0
6,7-dimethyl-8-ribityllumazine synthase
89287-46-7
Ribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1220-1224Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110145
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110146
Pays : United Kingdom
Organisme : Swiss National Science Foundation
ID : 176405
Pays : Switzerland
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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