3m99
From Proteopedia
Structure of the Ubp8-Sgf11-Sgf73-Sus1 SAGA DUB module
Structural highlights
FunctionSGF11_YEAST Component of the transcription regulatory histone acetylation (HAT) complex SAGA. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SGF11 is involved in transcriptional regulation of a subset of SAGA-regulated genes. Within the SAGA complex, participates in a subcomplex with SUS1, SGF73 and UBP8 required for deubiquitination of H2B and for the maintenance of steady-state H3 methylation levels. It is required to recruit UBP8 and SUS1 into the SAGA complex.[1] [2] 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 PubMedDeubiquitinating enzymes (DUBs) regulate diverse cellular functions by cleaving ubiquitin from specific protein substrates. How their activities are modulated in various cellular contexts remains poorly understood. The yeast deubiquitinase Ubp8 protein is recruited and activated by the SAGA complex and, together with Sgf11, Sus1, and Sgf73, forms a DUB module responsible for deubiquitinating histone H2B during gene expression. Here, we report the crystal structure of the complete SAGA DUB module, which features two functional lobes structurally coupled by Sgf73. In the "assembly lobe," a long Sgf11 N-terminal helix is clamped onto the Ubp8 ZnF-UBP domain by Sus1. In the "catalytic lobe," an Sgf11 C-terminal zinc-finger domain binds to the Ubp8 catalytic domain next to its active site. Our structural and functional analyses reveal a central role of Sgf11 and Sgf73 in activating Ubp8 for deubiquitinating histone H2B and demonstrate how a DUB can be allosterically regulated by its nonsubstrate partners. Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.,Kohler A, Zimmerman E, Schneider M, Hurt E, Zheng N Cell. 2010 May 14;141(4):606-17. Epub 2010 Apr 29. PMID:20434206[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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