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TitleSubnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms.
Journal, issue, pagesSci Adv, Vol. 9, Issue 6, Page eade2727, Year 2023
Publish dateFeb 10, 2023
AuthorsTara 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 /
PubMed AbstractParamyxoviruses-including important pathogens like parainfluenza, measles, and Nipah viruses-use a receptor binding protein [hemagglutinin-neuraminidase (HN) for parainfluenza] and a fusion protein ...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.
External linksSci Adv / PubMed:36763666 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution10.2 - 16.5 Å
Structure data

EMDB-27550: Subtomogram average of the HN/F fusion complex on authentic viral surfaces of HPIV3
Method: EM (subtomogram averaging) / Resolution: 10.2 Å

EMDB-27551: Subtomogram average of the PIA174 Fab/F complex on authentic viral surfaces of HPIV3
Method: EM (subtomogram averaging) / Resolution: 16.5 Å

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