1ZVD

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

Summary for 1ZVD

• Entry DOI: 10.2210/pdb1zvd/pdb
• Descriptor: Smad ubiquitination regulatory factor 2, SODIUM ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: ubiquitin ligasecatalytic mechanism, x-ray crystal structure, tgfbeta, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9HAU4
• Total number of polymer chains: 1
• Total formula weight: 44953.13

Authors

Ogunjimi, A.A.,Briant, D.J.,Pece-Barbara, N.,Le Roy, C.,Di Guglielmo, G.M.,Kavsak, P.,Rasmussen, R.K.,Seet, B.T.,Sicheri, F.,Wrana, J.L. (deposition date: 2005-06-01, release date: 2005-08-09, Last modification date: 2024-11-20)

Primary citation

Ogunjimi, A.A.,Briant, D.J.,Pece-Barbara, N.,Le Roy, C.,Di Guglielmo, G.M.,Kavsak, P.,Rasmussen, R.K.,Seet, B.T.,Sicheri, F.,Wrana, J.L.
Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT Domain.
Mol.Cell, 19:297-308, 2005

PubMed Abstract: 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.

PubMed: 16061177
DOI: 10.1016/j.molcel.2005.06.028

Experimental method

X-RAY DIFFRACTION (2.1 Å)