3o2p

A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)

Structural highlights 3o2p is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.233Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 PubMed In 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cullin 3D structures

spinqualitylabelsall models 3o2p, resolution 2.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image