Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12

Activation of the type I TGF beta receptor (T beta R-I) requires phosphoryl ation of a regulatory segment known as the GS region, located upstream of t he serine/threonine kinase domain in the cytoplasmic portion of the recepto r, The crystal structure of a fragment of unphosphorylated T beta R-I, cont aining both the GS region and the catalytic domain, has been determined in complex with the FK506-binding protein FKBP12. T beta R-I adopts an inactiv e conformation that is maintained by the unphosphorylated GS region, FKBP12 binds to the GS region of the receptor, capping the T beta R-II phosphoryl ation sites and further stabilizing the inactive conformation of T beta R-I . Certain structural features at the catalytic center of T beta R-I are cha racteristic of tyrosine kinases rather than Ser/Thr kinases.