This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ygs
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1ygs.jpg|left|200px]] | [[Image:1ygs.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1ygs", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | | | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | + | --> | |
| - | + | {{STRUCTURE_1ygs| PDB=1ygs | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''CRYSTAL STRUCTURE OF THE SMAD4 TUMOR SUPPRESSOR C-TERMINAL DOMAIN''' | '''CRYSTAL STRUCTURE OF THE SMAD4 TUMOR SUPPRESSOR C-TERMINAL DOMAIN''' | ||
| Line 30: | Line 27: | ||
[[Category: Pavletich, N P.]] | [[Category: Pavletich, N P.]] | ||
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: | + | [[Category: Beta-sandwich scaffold with a three-helix bundle]] |
| - | [[Category: | + | [[Category: Smad4]] |
| - | [[Category: | + | [[Category: Tgf-beta signal mediator]] |
| - | [[Category: | + | [[Category: Tumor suppressor c-terminal domain]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:17:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:17, 3 May 2008
CRYSTAL STRUCTURE OF THE SMAD4 TUMOR SUPPRESSOR C-TERMINAL DOMAIN
Overview
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.
About this Structure
1YGS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 16:17:55 2008
