1zvd

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{{STRUCTURE_1zvd| PDB=1zvd | SCENE= }}
{{STRUCTURE_1zvd| PDB=1zvd | SCENE= }}
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'''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''
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===Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16061177 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16061177}}
==About this Structure==
==About this Structure==
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[[Category: Tgfbeta]]
[[Category: Tgfbeta]]
[[Category: Ubiquitin ligasecatalytic mechanism,x-ray crystal structure]]
[[Category: Ubiquitin ligasecatalytic mechanism,x-ray crystal structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:07:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:41:56 2008''

Revision as of 12:41, 29 July 2008

Image:1zvd.png

Template:STRUCTURE 1zvd

Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain

Template:ABSTRACT PUBMED 16061177

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

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