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.
Guimond
A
A
Biotechnology Research Institute, National Research Council Canada, Montréal, Que.
Sulea
T
T
Pepin
M C
MC
O'Connor-McCourt
M D
MD
D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D001665:Binding Sites; D002478:Cells, Cultured; D003198:Computer Simulation; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II