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Cryo-EM structure of a Foamy Virus fusion glycoprotein stabilized in the prefusion conformation
Structural highlights
FunctionK7YEW5_9RETR The leader peptide is a component of released, infectious virions and is required for particle budding.[ARBA:ARBA00002261] The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.[ARBA:ARBA00024648] Publication Abstract from PubMedFoamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope (Env) glycoprotein drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immunodeficiency viruses from the subfamily of orthoretroviruses, which are only distantly related to the FVs. We report the cryo-electron microscopy structures of the FV Env ectodomain in the pre- and post-fusion states, which unexpectedly demonstrate structural similarity with the fusion protein (F) of paramyxo- and pneumoviruses, implying an evolutionary link between the viral fusogens. We describe the structural features that are unique to the FV Env and propose a mechanistic model for its conformational change, highlighting how the interplay of its structural elements could drive membrane fusion and viral entry. The structural knowledge on the FV Env now provides a framework for functional investigations, which can benefit the design of FV Env variants with improved features for use as gene therapy vectors. Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses.,Fernandez I, Bontems F, Brun D, Coquin Y, Goverde CA, Correia BE, Gessain A, Buseyne F, Rey FA, Backovic M Sci Adv. 2024 Oct 11;10(41):eado7035. doi: 10.1126/sciadv.ado7035. Epub 2024 Oct , 11. PMID:39392890[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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