3ong

Crystal structure of UBA2ufd-Ubc9: insights into E1-E2 interactions in Sumo pathways

spinqualitylabelsall models 3ong, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ong is a 4 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3onh Gene: UBA2, PIP2, UAL1, YDR390C, D9509.10 (ATCC 18824), UBC9, YDL064W (ATCC 18824) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [UBA2_YEAST] The dimeric enzyme acts as a SMT3 E1 ligase. It mediates ATP-dependent activation of SMT3 and formation of a thioester with a conserved cysteine residue on AOS1. [UBC9_YEAST] E2 ubiquitin-like--protein ligase mediating SUMO/Smt3 attachment to septins and PCNA. Seems to be involved in degradation of S- (CLB5) and M-phase cyclins (CLB2). Publication Abstract from PubMed Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2(ufd)), alone and in complex with Ubc9. The overall structures of both yeast Uba2(ufd) and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2(ufd)-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2(ufd)-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades. Crystal structure of UBA2(ufd)-Ubc9: insights into E1-E2 interactions in Sumo pathways.,Wang J, Taherbhoy AM, Hunt HW, Seyedin SN, Miller DW, Miller DJ, Huang DT, Schulman BA PLoS One. 2010 Dec 30;5(12):e15805. PMID:21209884 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SUMO conjugating enzyme Ubc9 Ubiquitin activating enzyme

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