1mr1

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|PDB= 1mr1 |SIZE=350|CAPTION= <scene name='initialview01'>1mr1</scene>, resolution 2.85&Aring;
|PDB= 1mr1 |SIZE=350|CAPTION= <scene name='initialview01'>1mr1</scene>, resolution 2.85&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=[[1ygs|1YGS]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mr1 OCA], [http://www.ebi.ac.uk/pdbsum/1mr1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mr1 RCSB]</span>
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}}
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==Overview==
==Overview==
The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.
The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.
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==Disease==
 
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Known diseases associated with this structure: 1p36 deletion syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164780 164780]], Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]], Polyposis, juvenile intestinal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]]
 
==About this Structure==
==About this Structure==
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[[Category: Wu, J W.]]
[[Category: Wu, J W.]]
[[Category: Zhang, F.]]
[[Category: Zhang, F.]]
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[[Category: ZN]]
 
[[Category: cancer]]
[[Category: cancer]]
[[Category: protein interaction]]
[[Category: protein interaction]]
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[[Category: tgf-b signaling]]
[[Category: tgf-b signaling]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:47:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:19:55 2008''

Revision as of 19:19, 30 March 2008


PDB ID 1mr1

Drag the structure with the mouse to rotate
, resolution 2.85Å
Ligands:
Related: 1YGS


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal Structure of a Smad4-Ski Complex


Overview

The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.

About this Structure

1MR1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling., Wu JW, Krawitz AR, Chai J, Li W, Zhang F, Luo K, Shi Y, Cell. 2002 Nov 1;111(3):357-67. PMID:12419246

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