Transient opening of trimeric prefusion RSV F proteins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31068578.
- Also identified by DOI 10.1038/s41467-019-09807-5 and PMC identifier 6506550.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Antibodies, Neutralizing
- Antibodies, Viral
- Respiratory Syncytial Virus, Human
- Viral Fusion Proteins