Mapping of putative binding sites on the ectodomain of the type II TGF-beta receptor by scanning-deletion mutagenesis and knowledge-based modeling.

Binding surfaces of the type II transforming growth factor (TGF)-beta receptor extracellular domain (TbetaRII-ECD) are mapped by combining scanning-deletion mutagenesis results with knowledge-based modeling of the ectodomain structure. Of the 17 deletion mutants produced within the core binding domain of TbetaRII-ECD, only three retained binding to TGF-beta. Comparative modeling based on the crystal structure of the activin type II receptor extracellular domain (ActRII-ECD) indicates that the TbetaRII mutants which retain TGF-beta binding are deleted in some of the loops connecting the beta-strands in the TbetaRII-ECD model. Interpretation of the mutagenesis data within the structural framework of the ectodomain model allows for the prediction of potential binding sites at the surface of TbetaRII-ECD.