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

Activation of the type I TGF beta receptor (T beta R-I) requires phosphorylation of a regulatory segment known as the GS region, located upstream of the serine/threonine kinase domain in the cytoplasmic portion of the receptor, The crystal structure of a fragment of unphosphorylated T beta R-I, containing 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 inactive conformation that is maintained by the unphosphorylated GS region, FKBP12 binds to the GS region of the receptor, capping the T beta R-II phosphorylation 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 characteristic of tyrosine kinases rather than Ser/Thr kinases.