Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 04 2023
26 04 2023
Historique:
received:
16
07
2022
accepted:
12
04
2023
medline:
28
4
2023
pubmed:
27
4
2023
entrez:
26
4
2023
Statut:
epublish
Résumé
Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.
Identifiants
pubmed: 37100772
doi: 10.1038/s41467-023-38015-5
pii: 10.1038/s41467-023-38015-5
pmc: PMC10132805
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2409Subventions
Organisme : Cancer Research UK
ID : 28159
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C68484/A28159
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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