Transient opening of trimeric prefusion RSV F proteins

Morgan S. A. Gilman, Polina Furmanova-Hollenstein, Gabriel Pascual, Angélique van ‘t Wout, Johannes P. M. Langedijk () and Jason S. McLellan ()
Additional contact information
Morgan S. A. Gilman: Geisel School of Medicine at Dartmouth
Polina Furmanova-Hollenstein: Janssen Infectious Diseases and Vaccines
Gabriel Pascual: Janssen Immunosciences, World Without Disease Accelerator
Angélique van ‘t Wout: Janssen Vaccines & Prevention B.V
Johannes P. M. Langedijk: Janssen Infectious Diseases and Vaccines
Jason S. McLellan: University of Texas at Austin

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract The respiratory syncytial virus (RSV) F glycoprotein is a class I fusion protein that mediates viral entry and is a major target of neutralizing antibodies. Structures of prefusion forms of RSV F, as well as other class I fusion proteins, have revealed compact trimeric arrangements, yet whether these trimeric forms can transiently open remains unknown. Here, we perform structural and biochemical studies on a recently isolated antibody, CR9501, and demonstrate that it enhances the opening of prefusion-stabilized RSV F trimers. The 3.3 Å crystal structure of monomeric RSV F bound to CR9501, combined with analysis of over 25 previously determined RSV F structures, reveals a breathing motion of the prefusion conformation. We also demonstrate that full-length RSV F trimers transiently open and dissociate on the cell surface. Collectively, these findings have implications for the function of class I fusion proteins, as well as antibody prophylaxis and vaccine development for RSV.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09807-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09807-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09807-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().