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A Dual E3 Mechanism for Rub1 Ligation to Cdc53
- Source :
- Molecular Cell. 39(5):784-796
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- In ubiquitin-like protein (UBL) cascades, a thioester-linked E2∼UBL complex typically interacts with an E3 enzyme for UBL transfer to the target. Here we demonstrate a variant mechanism, whereby the E2 Ubc12 functions with two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain. Hrt1 functions like a conventional RING E3, with its N terminus recruiting Cdc53 and C-terminal RING activating Ubc12∼Rub1. Dcn1's "potentiating neddylation" domain (Dcn1(P)) acts as an additional E3, reducing nonspecific Hrt1-mediated Ubc12∼Rub1 discharge and directing Ubc12's active site to Cdc53. Crystal structures of Dcn1(P)-Cdc53(WHB) and Ubc12 allow modeling of a catalytic complex, supported by mutational data. We propose that Dcn1's interactions with both Cdc53 and Ubc12 would restrict the otherwise flexible Hrt1 RING-bound Ubc12∼Rub1 to a catalytically competent orientation. Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target.
- Subjects :
- Models, Molecular
Saccharomyces cerevisiae Proteins
Materials science
Catalytic complex
Ubiquitin-Protein Ligases
Allosteric regulation
Saccharomyces cerevisiae
Crystallography, X-Ray
Article
03 medical and health sciences
0302 clinical medicine
Protein structure
Multienzyme Complexes
Ubiquitins
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
DNA ligase
SKP Cullin F-Box Protein Ligases
biology
Active site
Cell Biology
Cullin Proteins
Protein Structure, Tertiary
Biochemistry
chemistry
Ubiquitin ligase complex
biology.protein
Biophysics
Neddylation
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 39
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....ecb9e5b14705d63ff1ab09cd58ad6f98
- Full Text :
- https://doi.org/10.1016/j.molcel.2010.08.030