5C69

Crystal Structure of Prefusion-stabilized RSV F variant PR-DM

Summary for 5C69

• Entry DOI: 10.2210/pdb5c69/pdb
• Related: 4ZYP 5C6B
• Descriptor: Fusion glycoprotein F0,Fibritin, SULFATE ION, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (5 entities in total)
• Functional Keywords: class i viral fusion protein, fusion, respiratory syncytial virus, prefusion, viral protein
• Biological source: Human respiratory syncytial virus A; More
• Total number of polymer chains: 1
• Total formula weight: 55707.31

Authors

McLellan, J.S.,Langedijk, J.P.M. (deposition date: 2015-06-22, release date: 2015-09-23, Last modification date: 2024-10-23)

Primary citation

Krarup, A.,Truan, D.,Furmanova-Hollenstein, P.,Bogaert, L.,Bouchier, P.,Bisschop, I.J.,Widjojoatmodjo, M.N.,Zahn, R.,Schuitemaker, H.,McLellan, J.S.,Langedijk, J.P.
A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism.
Nat Commun, 6:8143-8143, 2015

PubMed Abstract: Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion RSV F elicits neutralizing antibodies in cotton rats and induces complete protection against viral challenge. Moreover, the structural and biochemical analysis of the prefusion variants suggests a function for p27, the excised segment that precedes the fusion peptide in the polypeptide chain.

PubMed: 26333350
DOI: 10.1038/ncomms9143

Experimental method

X-RAY DIFFRACTION (2.3 Å)