1zvd
From Proteopedia
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'''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain''' | '''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain''' | ||
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[[Category: Sicheri, F.]] | [[Category: Sicheri, F.]] | ||
[[Category: Wrana, J L.]] | [[Category: Wrana, J L.]] | ||
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| - | [[Category: | + | [[Category: Ubiquitin ligasecatalytic mechanism,x-ray crystal structure]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:07:15 2008'' | |
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Revision as of 15:07, 3 May 2008
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. 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 Sat May 3 18:07:15 2008
