1zvd
From Proteopedia
(New page: 200px<br /> <applet load="1zvd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zvd, resolution 2.10Å" /> '''Regulation of Smurf...) |
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| - | [[Image:1zvd.gif|left|200px]]<br /> | + | [[Image:1zvd.gif|left|200px]]<br /><applet load="1zvd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zvd" size=" | + | |
caption="1zvd, resolution 2.10Å" /> | caption="1zvd, resolution 2.10Å" /> | ||
'''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''<br /> | '''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The conjugation of ubiquitin to proteins involves a cascade of activating | + | The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Briant, D | + | [[Category: Briant, D J.]] |
| - | [[Category: Guglielmo, G | + | [[Category: Guglielmo, G M.Di.]] |
[[Category: Kavsak, P.]] | [[Category: Kavsak, P.]] | ||
| - | [[Category: Ogunjimi, A | + | [[Category: Ogunjimi, A A.]] |
[[Category: Pece-Barbara, N.]] | [[Category: Pece-Barbara, N.]] | ||
| - | [[Category: Rasmussen, R | + | [[Category: Rasmussen, R K.]] |
| - | [[Category: Roy, C | + | [[Category: Roy, C Le.]] |
| - | [[Category: Seet, B | + | [[Category: Seet, B T.]] |
[[Category: Sicheri, F.]] | [[Category: Sicheri, F.]] | ||
| - | [[Category: Wrana, J | + | [[Category: Wrana, J L.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: x-ray crystal structure]] | [[Category: x-ray crystal structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:26 2008'' |
Revision as of 14:19, 21 February 2008
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Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain
Overview
The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.
About this Structure
1ZVD is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain., Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL, Mol Cell. 2005 Aug 5;19(3):297-308. PMID:16061177
Page seeded by OCA on Thu Feb 21 16:19:26 2008
