Spatially resolved protein map of intact human cytomegalovirus virions.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
03
05
2022
accepted:
20
06
2023
medline:
31
8
2023
pubmed:
8
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
Herpesviruses assemble large enveloped particles that are difficult to characterize structurally due to their size, fragility and complex multilayered proteome with partially amorphous nature. Here we used crosslinking mass spectrometry and quantitative proteomics to derive a spatially resolved interactome map of intact human cytomegalovirus virions. This enabled the de novo allocation of 32 viral proteins into four spatially resolved virion layers, each organized by a dominant viral scaffold protein. The viral protein UL32 engages with all layers in an N-to-C-terminal radial orientation, bridging nucleocapsid to viral envelope. We observed the layer-specific incorporation of 82 host proteins, of which 39 are selectively recruited. We uncovered how UL32, by recruitment of PP-1 phosphatase, antagonizes binding to 14-3-3 proteins. This mechanism assures effective viral biogenesis, suggesting a perturbing role of UL32-14-3-3 interaction. Finally, we integrated these data into a coarse-grained model to provide global insights into the native configuration of virus and host protein interactions inside herpesvirions.
Identifiants
pubmed: 37550507
doi: 10.1038/s41564-023-01433-8
pii: 10.1038/s41564-023-01433-8
pmc: PMC10465357
doi:
Substances chimiques
Viral Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1732-1747Subventions
Organisme : Wellcome Trust
ID : 209250/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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