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1ygs

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1ygs, resolution 2.10Å ()
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


CRYSTAL STRUCTURE OF THE SMAD4 TUMOR SUPPRESSOR C-TERMINAL DOMAIN

Publication Abstract from PubMed

The Smad4/DPC4 tumour suppressor is inactivated in nearly half of pancreatic carcinomas and to a lesser extent in a variety of other cancers. Smad4/DPC4, and the related tumour suppressor Smad2, belong to the SMAD family of proteins that mediate signalling by the TGF-beta/activin/BMP-2/4 cytokine superfamily from receptor Ser/Thr protein kinases at the cell surface to the nucleus. SMAD proteins, which are phosphorylated by the activated receptor, propagate the signal, in part, through homo- and hetero-oligomeric interactions. Smad4/DPC4 plays a central role as it is the shared hetero-oligomerization partner of the other SMADs. The conserved carboxy-terminal domains of SMADs are sufficient for inducing most of the ligand-specific effects, and are the primary targets of tumorigenic inactivation. We now describe the crystal structure of the C-terminal domain (CTD) of the Smad4/DPC4 tumour suppressor, determined at 2.5 A resolution. The structure reveals that the Smad4/DPC4 CTD forms a crystallographic trimer through a conserved protein-protein interface, to which the majority of the tumour-derived missense mutations map. These mutations disrupt homo-oligomerization in vitro and in vivo, indicating that the trimeric assembly of the Smad4/DPC4 CTD is critical for signalling and is disrupted by tumorigenic mutations.

A structural basis for mutational inactivation of the tumour suppressor Smad4., Shi Y, Hata A, Lo RS, Massague J, Pavletich NP, Nature. 1997 Jul 3;388(6637):87-93. PMID:9214508

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1ygs is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Shi Y, Hata A, Lo RS, Massague J, Pavletich NP. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature. 1997 Jul 3;388(6637):87-93. PMID:9214508 doi:10.1038/40431

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