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 recep tor extracellular domain (T beta RII-ECD) are mapped by combining scanning- deletion mutagenesis results with knowledge-based modeling of the ectodomai n structure. Of the 17 deletion mutants produced within the core binding do main of T beta RII-ECD, only three retained binding to TGF-beta. Comparativ e modeling based on the crystal structure of the activin type II receptor e xtracellular domain (ActRII-ECD) indicates that the T beta RII mutants whic h retain TGF-beta binding are deleted in some of the loops connecting the b eta-strands in the T beta RII-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 T beta RII-ECD. (C ) 1999 Federation of European Biochemical Societies.