Identification of a functional site on the type I TGF‐β receptor by mutational analysis of its ectodomain

FEBS Letters

Zwaagstra, John C¹  O'Connor-McCourt, Maureen D¹  Sulea, Traian¹  Ekiel, Irena¹  Guimond, Alain¹ 

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

关键词: Type I transforming growth factor-β receptor ectodomain;    Mutagenesis;    Signaling;    Internalization;    Homology modeling;    Structure–function analysis;    TβRI-ECD;    type I TGF-β receptor ectodomain;    TβRII-ECD;    type II TGF-β receptor ectodomain;    TGF-β;    transforming growth factor-β;   

DOI  :  10.1016/S0014-5793(01)03231-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Six charged amino acid residues located in the ectodomain of the full-length type I transforming growth factor (TGF)-β receptor were individually mutated to alanine. Mutation of residues D47, D98, K102 and E104 resulted in functionally impaired receptors as demonstrated by a marked decrease in ligand-dependent signaling and ligand internalization relative to the wild-type receptor. The other two mutants (K39A and K87A) exhibited wild-type-like activity. Molecular modeling indicates that the four functionally important residues are located on the convex face of the ectodomain structure. Since mutation of these four residues affects signaling and ligand internalization but not ligand binding, we propose that this functional site is an interacting site between type I and II receptors.

【 授权许可】

Unknown