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

Cell. 1999 Feb 5;96(3):425-36. doi: 10.1016/s0092-8674(00)80555-3.

Abstract

Activation of the type I TGFbeta receptor (TbetaR-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 TbetaR-I, containing both the GS region and the catalytic domain, has been determined in complex with the FK506-binding protein FKBP12. TbetaR-I adopts an inactive conformation that is maintained by the unphosphorylated GS region. FKBP12 binds to the GS region of the receptor, capping the TbetaR-II phosphorylation sites and further stabilizing the inactive conformation of TbetaR-I. Certain structural features at the catalytic center of TbetaR-I are characteristic of tyrosine kinases rather than Ser/Thr kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type I*
  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Cytoplasm / chemistry
  • Cytoplasm / enzymology
  • Dimerization
  • Enzyme Activation
  • Humans
  • Immunophilins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Tyrosine Kinases / chemistry
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / chemistry*
  • Tacrolimus Binding Proteins

Substances

  • Peptide Fragments
  • Receptors, Transforming Growth Factor beta
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Tacrolimus Binding Proteins
  • Immunophilins

Associated data

  • PDB/1B6C