Structural Insights into the Assembly and Function of the SAGA Deubiquitinating Module

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Science  15 Apr 2010:
DOI: 10.1126/science.1190049


SAGA is a transcriptional coactivator complex that is conserved across eukaryotes and performs multiple functions during transcriptional activation and elongation. One role is deubiquitination of histone H2B, and this activity resides in a distinct subcomplex called the deubiquitinating module (DUBm), which contains the ubiquitin-specific protease, Ubp8, bound to Sgf11, Sus1, and Sgf73. The deubiquitinating activity depends on the presence of all four DUBm proteins. We report here the 1.90-angstrom resolution crystal structure of the DUB module bound to ubiquitin aldehyde, as well as the 2.45-angstrom resolution structure of the uncomplexed DUB module. The structure reveals an arrangement of protein domains that gives rise to a highly interconnected complex, which is stabilized by eight structural zinc atoms that are critical for enzymatic activity. The structure suggests a model for how interactions with the other DUBm proteins activate Ubp8 and allows us to speculate about how the DUB module binds to monoubiquitinated histone H2B in nucleosomes.