Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity

Yan, Ming; Wolberger, Cynthia

doi:10.1016/j.jmb.2014.12.004

Title: Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity

Journal Article · Tue Dec 16 23:00:00 EST 2014 · Journal of Molecular Biology

DOI: https://doi.org/10.1016/j.jmb.2014.12.004 · OSTI ID:1212204

Yan, Ming ^[1]; Wolberger, Cynthia ^[1]

Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine, Dept. of Biophysics and Biophysical Chemistry

The SAGA (Spt-Ada-Gcn5-acetyltransferase) complex performs multiple functions in transcription activation including deubiquitinating histone H2B, which is mediated by a subcomplex called the deubiquitinating module (DUBm). The yeast DUBm comprises a catalytic subunit, Ubp8, and three additional subunits, Sgf11, Sus1 and Sgf73, all of which are required for DUBm activity. A portion of the non-globular Sgf73 subunit lies between the Ubp8 catalytic domain and the ZnF-UBP domain and has been proposed to contribute to deubiquitinating activity by maintaining the catalytic domain in an active conformation. We report structural and solution studies of the DUBm containing two different Sgf73 point mutations that disrupt deubiquitinating activity. We find that the Sgf73 mutations abrogate deubiquitinating activity by impacting the Ubp8 ubiquitin-binding fingers region and have an unexpected effect on the overall folding and stability of the DUBm complex. Finally, taken together, our data suggest a role for Sgf73 in maintaining both the organization and ubiquitin-binding conformation of Ubp8, thereby contributing to overall DUBm activity.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1212204

Journal Information:: Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Journal Issue: 8 Vol. 427; ISSN 0022-2836

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Whole-Genome Sequencing of Suppressor DNA Mixtures Identifies Pathways That Compensate for Chromosome Segregation Defects in Schizosaccharomyces pombe Xu, Xingya; Wang, Li; Yanagida, Mitsuhiro G3: Genes\|Genomes\|Genetics, Vol. 8, Issue 3 https://doi.org/10.1534/g3.118.200048	journal	January 2018
Structural basis for histone H2B deubiquitination by the SAGA DUB module Morgan, M. T.; Haj-Yahya, M.; Ringel, A. E. Science, Vol. 351, Issue 6274 https://doi.org/10.1126/science.aac5681	journal	February 2016
Whole-Genome Sequencing of Suppressor DNA Mixtures Identifies Pathways That Compensate for Chromosome Segregation Defects in Schizosaccharomyces pombe Xu, Xingya; Wang, Li; Yanagida, Mitsuhiro G3: Genes\|Genomes\|Genetics, Vol. 8, Issue 3 https://doi.org/10.1534/g3.118.200048	journal	January 2018

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59 BASIC BIOLOGICAL SCIENCES
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