3o6b
From Proteopedia
A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB) low resolution
Structural highlights
Function[DCN1_YEAST] Required for neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity. Does not act by preventing deneddylation, but rather facilitates neddylation, possibly by acting with HRT1/RBX1 to recruit the Nedd8-charged E2 UBC12 to the cullin component of SCF-type complexes.[1] [CDC53_YEAST] Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The SCF complex associates with CDC34 as the E2 ubiquitin-conjugating enzyme. The functional specificity of the SCF complex depends on the type of F-box protein. SCF(CDC4) controls the G1-to-S phase transition; it directs ubiquitination of the phosphorylated CDK inhibitor SIC1 and of CDC6. SCF(CDC4) directs ubiquitination of GCN4. SCF(GRR1) directs ubiquitination of phosphorylated CLN1, CLN2 and GIC2. SCF(MET30) directs ubiquitination of MET4. SCF(DIA2) is specifically involved in the pheromone induced degradation of phosphorylated TEC1. SCF(MDM30) seems to direct ubiquitination of FZ01. Involved in the regulation of methionine biosynthesis genes.[2] [3] [4] [5] [6] [7] [8] [9] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn ubiquitin-like protein (UBL) cascades, a thioester-linked E2 approximately 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 approximately Rub1. Dcn1's "potentiating neddylation" domain (Dcn1(P)) acts as an additional E3, reducing nonspecific Hrt1-mediated Ubc12 approximately 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 approximately 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. A dual E3 mechanism for Rub1 ligation to Cdc53.,Scott DC, Monda JK, Grace CR, Duda DM, Kriwacki RW, Kurz T, Schulman BA Mol Cell. 2010 Sep 10;39(5):784-96. PMID:20832729[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Atcc 18824 | Duda, D M | Grace, C R.R | Kriwacki, R W | Kurz, T | Monda, J K | Schulman, B A | Scott, D C | Cell cycle | Ligase
