Structural and functional analysis of vaccinia viral fusion complex component protein A28 through NMR and molecular dynamic simulations.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
21
06
2023
accepted:
31
10
2023
revised:
22
11
2023
medline:
27
11
2023
pubmed:
10
11
2023
entrez:
10
11
2023
Statut:
epublish
Résumé
Host cell entry of vaccinia virus (a poxvirus) proceeds through multiple steps that involve many viral proteins to mediate cell infection. Upon binding to cells, vaccinia virus membrane fuses with host membranes via a viral entry fusion protein complex comprising 11 proteins: A16, A21, A28, F9, G3, G9, H2, J5, L1, L5 and O3. Despite vaccinia virus having two infectious forms, mature and enveloped, that have different membrane layers, both forms require an identical viral entry fusion complex for membrane fusion. Components of the poxvirus entry fusion complex that have been structurally assessed to date share no known homology with all other type I, II and III viral fusion proteins, and the large number of fusion protein components renders it a unique system to investigate poxvirus-mediated membrane fusion. Here, we determined the NMR structure of a truncated version of vaccinia A28 protein. We also expressed a soluble H2 protein and showed that A28 interacts with H2 protein at a 1:1 ratio in vitro. Furthermore, we performed extensive in vitro alanine mutagenesis to identify A28 protein residues that are critical for H2 binding, entry fusion complex formation, and virus-mediated membrane fusion. Finally, we used molecular dynamic simulations to model full-length A28-H2 subcomplex in membranes. In summary, we characterized vaccinia virus A28 protein and determined residues important in its interaction with H2 protein and membrane components. We also provide a structural model of the A28-H2 protein interaction to illustrate how it forms a 1:1 subcomplex on a modeled membrane.
Identifiants
pubmed: 37948471
doi: 10.1371/journal.ppat.1011500
pii: PPATHOGENS-D-23-01003
pmc: PMC10664964
doi:
Substances chimiques
Viral Fusion Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011500Informations de copyright
Copyright: © 2023 Kao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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