Ternary complex of transforming growth factor-beta1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily.

ABSTRACT: Transforming growth factor (TGF)-beta1, -beta2, and -beta3 are 25-kDa homodimeric polypeptides that play crucial nonoverlapping roles in embryogenesis, tissue development, carcinogenesis, and immune regulation. Here we report the 3.0-A resolution crystal structure of the ternary complex between human TGF-beta1 and the extracellular domains of its type I and type II receptors, TbetaRI and TbetaRII. The TGF-beta1 ternary complex structure is similar to previously reported TGF-beta3 complex except with a 10 degrees rotation in TbetaRI docking orientation. Quantitative binding studies showed distinct kinetics between the receptors and the isoforms of TGF-beta. TbetaRI showed significant binding to TGF-beta2 and TGF-beta3 but not TGF-beta1, and the binding to all three isoforms of TGF-beta was

SUBMITTER: Radaev S 

PROVIDER: S-EPMC2863181 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature