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

Journal Article · Wed Aug 18 04:00:00 EDT 2010 · Science

DOI:https://doi.org/10.1126/science.1190049· OSTI ID:1002495

Samara, Nadine L; Datta, Ajit B; Berndsen, Christopher E; Zhang, Xiangbin; Yao, Tingting; Cohen, Robert E; Wolberger, Cynthia ^[1]

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1. CSU

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 DUBm bound to ubiquitin aldehyde, as well as the 2.45 angstrom resolution structure of the uncomplexed DUBm. 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 DUBm binds to monoubiquitinated histone H2B in nucleosomes.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002495
• Journal Information: Science, Journal Name: Science Journal Issue: 05, 2010 Vol. 328; ISSN 0193-4511; ISSN SCEHDK
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ATOMS
CRYSTAL STRUCTURE
ELONGATION
HISTONES
NUCLEOSOMES
PROTEINS
RESOLUTION
ZINC