Journal Article PUBDB-2024-00334

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Spatially resolved protein map of intact human cytomegalovirus virions

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2023
Nature Publishing Group London

Nature microbiology 8(9), 1732 - 1747 () [10.1038/s41564-023-01433-8]
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Abstract: 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.

Classification:

Contributing Institute(s):
  1. CSSB-MHH-JB (CSSB-MHH-JB)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)
  2. DFG project 390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)
  3. SFB 958 A04 - Raumzeitliches Modell neuronaler Signaltransduktion und ihrer Regulation durch Präsynaptische Membrangerüste (A04) (202189827) (202189827)
  4. SFB 1114 C03/Erg. - Anomale Michaelis-Menten-Kinetik in dichtgepackter, heterogener Umgebung (C03/Erg.) (355497160) (355497160)
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Nature ; Essential Science Indicators ; IF >= 25 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record
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 Record created 2024-01-18, last modified 2025-07-24


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