2jqz
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Ubiquitination of proteins is an abundant modification that controls | + | 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== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Autoinhibition of the HECT- | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17719543 17719543] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Forman-Kay, J | + | [[Category: Forman-Kay, J D.]] |
| - | [[Category: Ogunjimi, A | + | [[Category: Ogunjimi, A A.]] |
[[Category: Rotin, D.]] | [[Category: Rotin, D.]] | ||
[[Category: Sicheri, F.]] | [[Category: Sicheri, F.]] | ||
[[Category: Wang, H.]] | [[Category: Wang, H.]] | ||
[[Category: Wiesner, S.]] | [[Category: Wiesner, S.]] | ||
| - | [[Category: Wrana, J | + | [[Category: Wrana, J L.]] |
[[Category: c2 domain]] | [[Category: c2 domain]] | ||
[[Category: phospholipid binding]] | [[Category: phospholipid binding]] | ||
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[[Category: ubiquitin protein ligase]] | [[Category: ubiquitin protein ligase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:05:16 2008'' |
Revision as of 16:05, 21 February 2008
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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 Thu Feb 21 18:05:16 2008
