Structural Basis for Postfusion-Specific Binding to the Respiratory Syncytial Virus F Protein by the Canonical Antigenic Site I Antibody 131–2a
peer-reviewed · ACS Infectious Diseases · 2025
| Date | 2025-08-08 |
| Type | peer-reviewed |
| Venue | ACS Infectious Diseases |
| Publisher | American Chemical Society (ACS) |
| Contribution | downstream-application |
| DOI | 10.1021/acsinfecdis.5c00368 |
| Citations (OpenAlex) | 4 |
Abstract
The respiratory syncytial virus (RSV) fusion (F) protein is a major target of antiviral antibodies following natural infection or vaccination and is responsible for mediating fusion between the viral envelope and the host membrane. The fusion process is driven by a large-scale conformational change in F, switching irreversibly from the metastable prefusion state to the stable postfusion conformation. Previous research has identified six distinct antigenic sites in RSV-F, termed sites Ø, I, II, III, IV, and V. Of these, only antigenic site I is fully specific to the postfusion conformation of F. A monoclonal antibody 131-2a that specifically targets postfusion F has been widely used as a research tool to probe for postfusion F and to define antigenic site I in serological studies, yet its sequence and precise epitope have remained unknown. Here, we use mass spectrometry-based de novo sequencing of 131-2a to reverse engineer a recombinant product and study the epitope to define antigenic site I with molecular detail, revealing the structural basis for the antibody’s specificity toward postfusion RSV-F.
Methods and tools
- RSV postfusion F antibody 131-2a sequencing: De novo MS sequencing of the widely used anti-RSV-F antibody 131-2a enabled a recombinant version and a structure explaining its postfusion specificity.
Methods it uses
- PEAKS: Commercial DP-based de novo