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

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Abstract
Binding surfaces of the type II transforming growth factor (TGF)‐β receptor extracellular domain (TβRII‐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 TβRII‐ECD, only three retained binding to TGF‐β. Comparative modeling based on the crystal structure of the activin type II receptor extracellular domain (ActRII‐ECD) indicates that the TβRII mutants which retain TGF‐β binding are deleted in some of the loops connecting the β‐strands in the TβRII‐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 TβRII‐ECD.