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

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:
 [1] ;  [1]
  1. Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine, Dept. of Biophysics and Biophysical Chemistry
Publication Date:
OSTI Identifier:
1212204
Grant/Contract Number:
AC02-06CH11357; GM-095822
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
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Sgf73; SAGA; Ubp8; deubiquitinating enzyme; transcription activation