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1dd1
From Proteopedia
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| - | [[Image:1dd1.gif|left|200px]] | + | [[Image:1dd1.gif|left|200px]] |
| - | + | ||
| - | '''CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT''' | + | {{Structure |
| + | |PDB= 1dd1 |SIZE=350|CAPTION= <scene name='initialview01'>1dd1</scene>, resolution 2.62Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DD1 is a [ | + | 1DD1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DD1 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of a transcriptionally active Smad4 fragment., Qin B, Lam SS, Lin K, Structure. 1999 Dec 15;7(12):1493-503. PMID:[http:// | + | Crystal structure of a transcriptionally active Smad4 fragment., Qin B, Lam SS, Lin K, Structure. 1999 Dec 15;7(12):1493-503. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10647180 10647180] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: b-sheet sandwich helix-turn-helix]] | [[Category: b-sheet sandwich helix-turn-helix]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:36:32 2008'' |
Revision as of 08:36, 20 March 2008
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| , resolution 2.62Å | |||||||
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| Ligands: | |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT
Contents |
Overview
BACKGROUND: Smad4 functions as a common mediator of transforming growth factor beta (TGF-beta) signaling by forming complexes with the phosphorylated state of pathway-restricted SMAD proteins that act in specific signaling pathways to activate transcription. SMAD proteins comprise two domains, the MH1 and MH2 domain, separated by a linker region. The transcriptional activity and synergistic effect of Smad4 require a stretch of proline-rich sequence, the SMAD-activation domain (SAD), located N-terminal of the MH2 domain. To understand how the SAD contributes to Smad4 function, the crystal structure of a fragment including the SAD and MH2 domain (S4AF) was determined. RESULTS: The structure of the S4AF trimer reveals novel features important for Smad4 function. A Smad4-specific sequence insertion within the MH2 domain interacts with the C-terminal tail to form a structural extension from the core. This extension (the TOWER) contains a solvent-accessible glutamine-rich helix. The SAD reinforces the TOWER and the structural core through interactions; two residues involved in these interactions are targets of tumorigenic mutation. The solvent-accessible proline residues of the SAD are located on the same face as the glutamine-rich helix of the TOWER, forming a potential transcription activation surface. A tandem sulfate-ion-binding site was identified within the subunit interface, which may interact with the phosphorylated C-terminal sequence of pathway-restricted SMAD proteins. CONCLUSIONS: The structure suggests that the SAD provides transcriptional capability by reinforcing the structural core and coordinating with the TOWER to present the proline-rich and glutamine-rich surfaces for interaction with transcription partners. The sulfate-ion-binding sites are potential 'receptors' for the phosphorylated sequence of pathway-restricted SMAD proteins in forming a heteromeric complex. The structure thus provides a new model that can be tested using biochemical and cellular approaches.
Disease
Known diseases associated with this structure: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome OMIM:[600993], Pancreatic cancer OMIM:[600993], Polyposis, juvenile intestinal OMIM:[600993]
About this Structure
1DD1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of a transcriptionally active Smad4 fragment., Qin B, Lam SS, Lin K, Structure. 1999 Dec 15;7(12):1493-503. PMID:10647180
Page seeded by OCA on Thu Mar 20 10:36:32 2008
