Transient opening of trimeric prefusion RSV F proteins.
Nat Commun
; 10(1): 2105, 2019 05 08.
Article
in En
| MEDLINE
| ID: mdl-31068578
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Fusion Proteins
/
Respiratory Syncytial Virus, Human
/
Antibodies, Neutralizing
/
Antibodies, Viral
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2019
Document type:
Article
Affiliation country: