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Mapping of putative binding sites on the ectodomain of the type II TGF‐β receptor by scanning‐deletion mutagenesis and knowledge‐based modeling
Author(s) -
Guimond Alain,
Sulea Traian,
Pepin Marie-Claude,
O'Connor-McCourt Maureen D
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00869-8
Subject(s) - ectodomain , mutagenesis , acvr2b , binding site , mutant , site directed mutagenesis , receptor–ligand kinetics , biology , alanine scanning , plasma protein binding , receptor , microbiology and biotechnology , chemistry , tgf beta signaling pathway , biophysics , biochemistry , gene
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.