1KHX

Crystal structure of a phosphorylated Smad2

Summary for 1KHX

• Entry DOI: 10.2210/pdb1khx/pdb
• Related: 1DEV
• Descriptor: Smad2 (2 entities in total)
• Functional Keywords: tgf-beta signaling, smad2, phosphorylation, receptor kinase signaling, cancer, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q15796
• Total number of polymer chains: 1
• Total formula weight: 25540.67

Authors

Wu, J.-W.,Hu, M.,Chai, J.,Seoane, J.,Huse, M.,Kyin, S.,Muir, T.W.,Fairman, R.,Massague, J.,Shi, Y. (deposition date: 2001-12-01, release date: 2002-02-06, Last modification date: 2024-11-20)

Primary citation

Wu, J.W.,Hu, M.,Chai, J.,Seoane, J.,Huse, M.,Li, C.,Rigotti, D.J.,Kyin, S.,Muir, T.W.,Fairman, R.,Massague, J.,Shi, Y.
Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.
Mol.Cell, 8:1277-1289, 2001

PubMed Abstract: Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.

PubMed: 11779503
DOI: 10.1016/S1097-2765(01)00421-X

Experimental method

X-RAY DIFFRACTION (1.8 Å)