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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activin Receptors, Type I*
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Amino Acid Sequence
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Crystallography, X-Ray
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Cytoplasm / chemistry
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Cytoplasm / enzymology
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Dimerization
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Enzyme Activation
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Humans
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Immunophilins / chemistry*
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / chemistry*
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Protein Conformation
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Protein Serine-Threonine Kinases / chemistry*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / chemistry
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / chemistry*
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Tacrolimus Binding Proteins
Substances
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Peptide Fragments
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Receptors, Transforming Growth Factor beta
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Tacrolimus Binding Proteins
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Immunophilins