Crystal structure of murine/human Ubc9 provides insight into the variability of the ubiquitin-conjugating system.
Murine/human ubiquitin-conjugating enzyme Ubc9 is a functional homolog of Saccharomyces cerevisiae Ubc9 that is essential for the viability of yeast cells with a specific role in the G2-M transition of the cell cycle. The structure of recombinant mammalian Ubc9 has been determined from two crystal forms at 2.0 A resolution. Like Arabidopsis thaliana Ubc1 and S. cerevisiae Ubc4, murine/human Ubc9 was crystallized as a monomer, suggesting that previously reported hetero- and homo-interactions among Ubcs may be relatively weak or indirect. Compared with the known crystal structures of Ubc1 and Ubc4, which regulate different cellular processes, Ubc9 has a 5-residue insertion that forms a very exposed tight beta-hairpin and a 2-residue insertion that forms a bulge in a loop close to the active site. Mammalian Ubc9 also possesses a distinct electrostatic potential distribution that may provide possible clues to its remarkable ability to interact with other proteins. The 2-residue insertion and other sequence and structural heterogeneity observed at the catalytic site suggest that different Ubcs may utilize catalytic mechanisms of varying efficiency and substrate specificity.
Tong
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Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Hateboer
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G
Perrakis
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A
Bernards
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R
Sixma
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TK
D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins; D001665:Binding Sites; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000648:ultrastructure; D006801:Humans; D008025:Ligases / Q000648:ultrastructure*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D029681:Arabidopsis Proteins; D005656:Fungal Proteins; D010940:Plant Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C489357:UBC1 protein, Arabidopsis; C066752:UBC1 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; C063109:ubiquitin-conjugating enzyme UBC4; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9