Site-directed mutagenesis of the type II TGF-beta receptor indicates a ligand-binding site distinct from that of the type II activin receptor.
Site-directed mutagenesis was used to map the ligand-binding surface of the type II transforming growth factor-beta receptor extracellular domain (TbetaRII-ECD). Two putative ligand-binding sites were probed, the first being a predicted hydrophobic patch, the second being the finger 1 surface loop. Nine residues were mutated in the context of full-length TbetaRII and the effect of these mutations on ligand-binding and receptor signaling was analyzed. Complementary information was obtained by examining 'natural' evolutionary TbetaRII mutations. Together, the results indicate that residues within the finger 1 region, but not the hydrophobic patch, of the TbetaRII-ECD are required for productive ligand-binding. We conclude that, surprisingly, the ECDs of TbetaRII and type II activin receptor utilize distinct interacting surfaces for binding their respective ligands.
Guimond
Alain
A
Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, H4P 2R2, Montréal, QC, Canada.
Sulea
Traian
T
Pen
Ally
A
Ear
Pohien
P
O'Connor-McCourt
Maureen D
MD
D030301:Activin Receptors, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D004268:DNA-Binding Proteins; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030301:Activin Receptors, Type II; D000077294:Receptor, Transforming Growth Factor-beta Type II; C425585:activin receptor type II-A