1IAS

CYTOPLASMIC DOMAIN OF UNPHOSPHORYLATED TYPE I TGF-BETA RECEPTOR CRYSTALLIZED WITHOUT FKBP12

Summary for 1IAS

• Entry DOI: 10.2210/pdb1ias/pdb
• Related: 1b6c
• Descriptor: TGF-BETA RECEPTOR TYPE I, SULFATE ION (2 entities in total)
• Functional Keywords: kinase, tgf-beta receptor, gs region, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P36897
• Total number of polymer chains: 5
• Total formula weight: 196044.15

Authors

Huse, M.,Muir, T.W.,Chen, Y.-G.,Kuriyan, J.,Massague, J. (deposition date: 2001-03-23, release date: 2001-10-03, Last modification date: 2024-04-03)

Primary citation

Huse, M.,Muir, T.W.,Xu, L.,Chen, Y.G.,Kuriyan, J.,Massague, J.
The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
Mol.Cell, 8:671-682, 2001

PubMed Abstract: The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the GS region, a conserved juxtamembrane segment located just N-terminal to the kinase domain. We have studied the molecular mechanism of receptor activation using a homogeneously tetraphosphorylated form of T beta R-I, prepared using protein semisynthesis. Phosphorylation of the GS region dramatically enhances the specificity of T beta R-I for the critical C-terminal serines of Smad2. In addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a phosphorylation-dependent manner and is no longer recognized by the inhibitory protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS region from a binding site for an inhibitor into a binding surface for substrate. Our observations suggest that phosphoserine/phosphothreonine-dependent localization is a key feature of the T beta R-I/Smad activation process.

PubMed: 11583628
DOI: 10.1016/S1097-2765(01)00332-X

Experimental method

X-RAY DIFFRACTION (2.9 Å)