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Site‐directed mutagenesis of the type II TGF‐β receptor indicates a ligand‐binding site distinct from that of the type II activin receptor
Author(s) -
Guimond Alain,
Sulea Traian,
Pen Ally,
Ear Pohien,
O'Connor-McCourt Maureen D
Publication year - 2002
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(02)02378-5
Subject(s) - acvr2b , binding site , ligand (biochemistry) , site directed mutagenesis , receptor , mutagenesis , activin receptor , activin type 2 receptors , biology , chemistry , biophysics , tgf beta signaling pathway , biochemistry , mutation , mutant , gene
Site‐directed mutagenesis was used to map the ligand‐binding surface of the type II transforming growth factor‐β receptor extracellular domain (TβRII‐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 TβRII and the effect of these mutations on ligand‐binding and receptor signaling was analyzed. Complementary information was obtained by examining ‘natural’ evolutionary TβRII mutations. Together, the results indicate that residues within the finger 1 region, but not the hydrophobic patch, of the TβRII‐ECD are required for productive ligand‐binding. We conclude that, surprisingly, the ECDs of TβRII and type II activin receptor utilize distinct interacting surfaces for binding their respective ligands.