Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity
Abstract
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.
- Authors:
-
- Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine, Dept. of Biophysics and Biophysical Chemistry
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1212204
- Alternate Identifier(s):
- OSTI ID: 1367765
- Grant/Contract Number:
- AC02-06CH11357; GM-095822
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Molecular Biology
- Additional Journal Information:
- Journal Volume: 427; Journal Issue: 8; Journal ID: ISSN 0022-2836
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Sgf73; SAGA; Ubp8; deubiquitinating enzyme; transcription activation
Citation Formats
Yan, Ming, and Wolberger, Cynthia. Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity. United States: N. p., 2014.
Web. doi:10.1016/j.jmb.2014.12.004.
Yan, Ming, & Wolberger, Cynthia. Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity. United States. https://doi.org/10.1016/j.jmb.2014.12.004
Yan, Ming, and Wolberger, Cynthia. Wed .
"Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity". United States. https://doi.org/10.1016/j.jmb.2014.12.004. https://www.osti.gov/servlets/purl/1212204.
@article{osti_1212204,
title = {Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity},
author = {Yan, Ming and Wolberger, Cynthia},
abstractNote = {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.},
doi = {10.1016/j.jmb.2014.12.004},
journal = {Journal of Molecular Biology},
number = 8,
volume = 427,
place = {United States},
year = {Wed Dec 17 00:00:00 EST 2014},
month = {Wed Dec 17 00:00:00 EST 2014}
}
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