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

Tara C. Marcink, Gillian Zipursky, Wenjing Cheng, Kyle Stearns, Shari Stenglein, Kate Golub, Frances Cohen, Francesca Bovier, Daniel Pfalmer, Alexander L. Greninger, Matteo Porotto, Amedee des Georges, Anne Moscona

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbereade2727
JournalScience Advances
Issue number6
StatePublished - Feb 2023

ASJC Scopus subject areas

  • General


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