Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain
| Autor: | Abiodun A. Ogunjimi, Bruce T. Seet, Richele K. Rasmussen, Gianni M. Di Guglielmo, Douglas J. Briant, Christine Le Roy, Peter A. Kavsak, Jeffrey L. Wrana, Frank Sicheri, Nadia Pece-Barbara |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
HECT domain
Models Molecular Receptor complex Ubiquitin-Protein Ligases Amino Acid Motifs Molecular Sequence Data macromolecular substances Ubiquitin-Activating Enzymes Crystallography X-Ray Transfection Catalysis Domain (software engineering) Cell Line Smad7 Protein Ubiquitin Humans Amino Acid Sequence Molecular Biology chemistry.chemical_classification DNA ligase Binding Sites biology Sequence Homology Amino Acid Mutagenesis Cell Biology Peptide Fragments Recombinant Proteins Ubiquitin ligase Protein Structure Tertiary DNA-Binding Proteins Enzyme Activation Enzyme chemistry Biochemistry Mutation Ubiquitin-Conjugating Enzymes biology.protein Mutagenesis Site-Directed Trans-Activators Receptors Transforming Growth Factor beta Protein Binding Signal Transduction |
| Zdroj: | Molecular cell. 19(3) |
| ISSN: | 1097-2765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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