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Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms

Paramyxoviruses—including important pathogens like parainfluenza, measles, and Nipah viruses—use a receptor binding protein [hemagglutinin-neuraminidase (HN) for parainfluenza] and a fusion protein (F), acting in a complex, to enter cells. We use cryo–electron tomography to visualize the fusion comp...

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Detalles Bibliográficos
Autores principales: Marcink, Tara C., Zipursky, Gillian, Cheng, Wenjing, Stearns, Kyle, Stenglein, Shari, Golub, Kate, Cohen, Frances, Bovier, Francesca, Pfalmer, Daniel, Greninger, Alexander L., Porotto, Matteo, des Georges, Amedee, Moscona, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917000/
https://www.ncbi.nlm.nih.gov/pubmed/36763666
http://dx.doi.org/10.1126/sciadv.ade2727
Descripción
Sumario:Paramyxoviruses—including important pathogens like parainfluenza, measles, and Nipah viruses—use a receptor binding protein [hemagglutinin-neuraminidase (HN) for parainfluenza] and a fusion protein (F), acting in a complex, to enter cells. We use cryo–electron tomography to visualize the fusion complex of human parainfluenza virus 3 (HN/F) on the surface of authentic clinical viruses at a subnanometer resolution sufficient to answer mechanistic questions. An HN loop inserts in a pocket on F, showing how the fusion complex remains in a ready but quiescent state until activation. The globular HN heads are rotated with respect to each other: one downward to contact F, and the other upward to grapple cellular receptors, demonstrating how HN/F performs distinct steps before F activation. This depiction of viral fusion illuminates potentially druggable targets for paramyxoviruses and sheds light on fusion processes that underpin wide-ranging biological processes but have not been visualized in situ or at the present resolution.