2jqz
From Proteopedia
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[[Image:2jqz.jpg|left|200px]] | [[Image:2jqz.jpg|left|200px]] | ||
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'''Solution Structure of the C2 domain of human Smurf2''' | '''Solution Structure of the C2 domain of human Smurf2''' | ||
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[[Category: Wiesner, S.]] | [[Category: Wiesner, S.]] | ||
[[Category: Wrana, J L.]] | [[Category: Wrana, J L.]] | ||
| - | [[Category: | + | [[Category: C2 domain]] |
| - | [[Category: | + | [[Category: Phospholipid binding]] |
| - | [[Category: | + | [[Category: Smurf2]] |
| - | [[Category: | + | [[Category: Ubiquitin protein ligase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:12:06 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:12, 4 May 2008
Solution Structure of the C2 domain of human Smurf2
Overview
Ubiquitination of proteins is an abundant modification that controls numerous cellular processes. Many Ubiquitin (Ub) protein ligases (E3s) target both their substrates and themselves for degradation. However, the mechanisms regulating their catalytic activity are largely unknown. The C2-WW-HECT-domain E3 Smurf2 downregulates transforming growth factor-beta (TGF-beta) signaling by targeting itself, the adaptor protein Smad7, and TGF-beta receptor kinases for degradation. Here, we demonstrate that an intramolecular interaction between the C2 and HECT domains inhibits Smurf2 activity, stabilizes Smurf2 levels in cells, and similarly inhibits certain other C2-WW-HECT-domain E3s. Using NMR analysis the C2 domain was shown to bind in the vicinity of the catalytic cysteine, where it interferes with Ub thioester formation. The HECT-binding domain of Smad7, which activates Smurf2, antagonizes this inhibitory interaction. Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells.
About this Structure
2JQZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain., Wiesner S, Ogunjimi AA, Wang HR, Rotin D, Sicheri F, Wrana JL, Forman-Kay JD, Cell. 2007 Aug 24;130(4):651-62. PMID:17719543 Page seeded by OCA on Sun May 4 09:12:06 2008
