Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Structure. 2012 Aug 8;20(8):1414-24. doi: 10.1016/j.str.2012.05.015. Epub 2012 Jul 5.

A role for intersubunit interactions in maintaining SAGA deubiquitinating module structure and activity.

Author information

  • 1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205-2185, USA.


The deubiquitinating module (DUBm) of the SAGA coactivator contains the Ubp8 isopeptidase, Sgf11, Sus1, and Sgf73, which form a highly interconnected complex. Although Ubp8 contains a canonical USP catalytic domain, it is only active when in complex with the other DUBm subunits. The Sgf11 zinc finger (Sgf11-ZnF) binds near the Ubp8 active site and is essential for full activity, suggesting that the Sgf11-ZnF helps maintain the active conformation of Ubp8. We report structural and solution studies showing that deletion of the Sgf11-ZnF destabilizes incorporation of Ubp8 within the DUBm, giving rise to domain swapping with a second complex and misaligning active site residues. Activating mutations in Ubp8 that partially restore activity in the absence of the Sgf11-ZnF promote the monomeric form of the DUBm. Our data suggest an unexpected role for Sgf11 in compensating for the absence of structural features that maintain the active conformation of Ubp8.

Copyright © 2012 Elsevier Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk