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| - | [[Image:1dd1.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1dd1| PDB=1dd1 | SCENE= }} | | {{STRUCTURE_1dd1| PDB=1dd1 | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT'''
| + | ===CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10647180}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10647180 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10647180}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Qin, B Y.]] | | [[Category: Qin, B Y.]] |
| | [[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 Fri May 2 13:42:32 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:50:35 2008'' |
Revision as of 19:50, 30 June 2008
Template:STRUCTURE 1dd1
CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT
Template:ABSTRACT PUBMED 10647180
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 Mon Jun 30 22:50:35 2008
