6OE4

Prefusion RSV F monomer bound by neutralizing antibody CR9501

Summary for 6OE4

• Entry DOI: 10.2210/pdb6oe4/pdb
• Descriptor: Fusion glycoprotein F0, CR9501 Fab Light Chain, CR9501 Fab Heavy Chain, ... (4 entities in total)
• Functional Keywords: class i fusion protein, immunoglobulin, respiratory syncytial virus, trimerization, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human respiratory syncytial virus A (strain A2); More
• Total number of polymer chains: 6
• Total formula weight: 212045.98

Authors

McLellan, J.S.,Gilman, M.S.A. (deposition date: 2019-03-27, release date: 2019-04-17, Last modification date: 2024-11-20)

Primary citation

Gilman, M.S.A.,Furmanova-Hollenstein, P.,Pascual, G.,B van 't Wout, A.,Langedijk, J.P.M.,McLellan, J.S.
Transient opening of trimeric prefusion RSV F proteins.
Nat Commun, 10:2105-2105, 2019

PubMed 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.

PubMed: 31068578
DOI: 10.1038/s41467-019-09807-5

Experimental method

X-RAY DIFFRACTION (3.3 Å)