Harnessing AlphaFold3 to Elucidate BBSome Structure and Protein Partners - PubMed
10 hours ago
- #BBSome
- #protein-interactions
- #AlphaFold3
- AlphaFold3 generated a structural model of the BBSome complex that closely matches recent cryo-EM data (Cα RMSD: 1.203 Å).
- BBS1 and BBS9 were identified as central interaction hubs, BBS2 and BBS7 showed the most polar contacts, and the pathogenic mutation BBS1M390R was predicted to destabilize the complex.
- BBS4 stably interacts with pericentriolar material 1, suggesting a role in centriolar satellite localization.
- Interaction analysis with GPCRs identified contact hotspots on BBS1, BBS4, and BBS5, supported by immunoprecipitation and peptide competition assays.
- Modeling suggested plausible interfaces between specific BBS proteins and metabolic signaling proteins (e.g., MRAP2, leptin receptor, insulin receptor), aligning with reported biochemical associations.
- The findings provide new insights into BBSome structure and receptor interactions, offering a predictive framework for exploring its role in ciliary trafficking and human disease.