8YE3

Cryo-EM structure of human respiratory syncytial virus fusion protein variant

This is a non-PDB format compatible entry.

Summary for 8YE3

• Entry DOI: 10.2210/pdb8ye3/pdb
• EMDB information: 39188
• Descriptor: Fusion glycoprotein F0 (1 entity in total)
• Functional Keywords: rsv, fusion glycoprotein, pre-fusion, viral protein
• Biological source: human respiratory syncytial virus; More
• Total number of polymer chains: 3
• Total formula weight: 164403.84

Authors

Li, Q.M.,Su, J.G.,Zhang, J.,Liang, Y.,Shao, S.,Li, X.Y.,Zhao, Z.X. (deposition date: 2024-02-21, release date: 2024-10-02, Last modification date: 2024-11-06)

Primary citation

Liang, Y.,Shao, S.,Li, X.Y.,Zhao, Z.X.,Liu, N.,Liu, Z.M.,Shen, F.J.,Zhang, H.,Hou, J.W.,Zhang, X.F.,Jin, Y.Q.,Du, L.F.,Li, X.,Zhang, J.,Su, J.G.,Li, Q.M.
Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.
Science, 385:1484-1491, 2024

PubMed Abstract: The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.

PubMed: 39325881
DOI: 10.1126/science.adp2362

Experimental method

ELECTRON MICROSCOPY (3.4 Å)