1r4n

APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATPAPPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATP

Structural highlights 1r4n is a 12 chain structure with sequence from Homo sapiens. The December 2004 RCSB PDB Molecule of the Month feature on Ubiquitin by David S. Goodsell is 10.2210/rcsb_pdb/mom_2004_12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.6Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ULA1_HUMAN Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. 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 E1 enzymes initiate ubiquitin-like protein (ubl) transfer cascades by catalyzing adenylation of the ubl's C terminus. An E1's selectivity for its cognate ubl is essential because the E1 subsequently coordinates the ubl with its correct downstream pathway. We report here the structure of the 120 kDa quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP. The E1 selectively recruits NEDD8 through a bipartite interface, involving a domain common to all ubl activating enzymes including bacterial ancestors, and also eukaryotic E1-specific sequences. By modeling ubiquitin into the NEDD8 binding site and performing mutational analysis, we identify a single conserved arginine in APPBP1-UBA3 that acts as a selectivity gate, preventing misactivation of ubiquitin by NEDD8's E1. NEDD8 residues that interact with E1 correspond to residues in ubiquitin important for binding the proteasome and other ubiquitin-interacting proteins, suggesting that the conjugation and recognition machineries have coevolved for each specific ubl. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.,Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL Jr, Holton JM, Schulman BA Mol Cell. 2003 Dec;12(6):1427-37. PMID:14690597 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also NEDD8 3D structures of Ubiquitin activating enzyme

spinqualitylabelsall models 1r4n, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image