1zvd
From Proteopedia
OCA (Talk | contribs)
(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...)
Next diff →
Revision as of 18:35, 12 November 2007
|
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 NA and PO4 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 Mon Nov 12 20:41:50 2007
