Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

- A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein.
- Transfected SH and BAP31 co-localize in lung epithelial cells.
- Endogenous BAP31 is pulled down by RSV SH protein.
- BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles.
- This interaction is proposed to be a potential drug target.

The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target.