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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Animals
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Antibodies, Neutralizing / chemistry
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Antibodies, Neutralizing / immunology
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Antibodies, Neutralizing / metabolism*
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Antibodies, Viral / chemistry
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Antibodies, Viral / immunology
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Antibodies, Viral / metabolism*
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B-Lymphocytes / virology
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Chlorocebus aethiops
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Computer Simulation
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Crystallography, X-Ray
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Drug Development
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HEK293 Cells
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HeLa Cells
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Humans
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Models, Molecular
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Protein Multimerization / physiology
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Respiratory Syncytial Virus Infections / immunology
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Respiratory Syncytial Virus Infections / prevention & control
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Respiratory Syncytial Virus Infections / virology
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Respiratory Syncytial Virus Vaccines / immunology
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Respiratory Syncytial Virus, Human / isolation & purification
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Respiratory Syncytial Virus, Human / physiology*
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Vero Cells
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Viral Fusion Proteins / chemistry
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Viral Fusion Proteins / immunology
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Viral Fusion Proteins / metabolism*
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Respiratory Syncytial Virus Vaccines
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Viral Fusion Proteins