Site‐directed mutagenesis of the type II TGF‐β receptor indicates a ligand‐binding site distinct from that of the type II activin receptor

FEBS Letters

O'Connor-McCourt, Maureen D¹  Sulea, Traian¹  Pen, Ally¹  Ear, Pohien¹  Guimond, Alain¹ 

[1] Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, QC H4P 2R2, Canada

关键词: Type II transforming growth factor-β receptor ectodomain;    Mutagenesis;    Ligand-binding;    Signaling;    Structure–function analysis;    Type II activin receptor;    TGF-β;    transforming growth factor-β;    TβRII;    type II TGF-β receptor;    ActRII;    type II activin receptor;    ECD;    ectodomain;   

DOI  :  10.1016/S0014-5793(02)02378-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown