Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B
Zeev-Ben-Mordehai, T. and Vasishtan, D. and Hernández Durán, A. and Vollmer, B. and White, P. and Prasad Pandurangan, A. and Siebert, C.A. and Topf, Maya and Grünewald, K. (2016) Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B. Proceedings of the National Academy of Sciences of the United States of America 113 (15), pp. 4176-4181. ISSN 0027-8424.
Abstract
Many viruses are enveloped by a lipid bilayer acquired during assembly, which is typically studded with one or two types of glycoproteins. These viral surface proteins act as the primary interface between the virus and the host. Entry of enveloped viruses relies on specialized fusogen proteins to help merge the virus membrane with the host membrane. In the multicomponent herpesvirus fusion machinery, glycoprotein B (gB) acts as this fusogen. Although the structure of the gB ectodomain postfusion conformation has been determined, any other conformations (e.g., prefusion, intermediate conformations) have so far remained elusive, thus restricting efforts to develop antiviral treatments and prophylactic vaccines. Here, we have characterized the full-length herpes simplex virus 1 gB in a native membrane by displaying it on cell-derived vesicles and using electron cryotomography. Alongside the known postfusion conformation, a novel one was identified. Its structure, in the context of the membrane, was determined by subvolume averaging and found to be trimeric like the postfusion conformation, but appeared more condensed. Hierarchical constrained density-fitting of domains unexpectedly revealed the fusion loops in this conformation to be apart and pointing away from the anchoring membrane. This vital observation is a substantial step forward in understanding the complex herpesvirus fusion mechanism, and opens up new opportunities for more targeted intervention of herpesvirus entry.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 14 Apr 2016 08:02 |
| Last Modified: | 02 Aug 2023 17:23 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/14937 |
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