Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2010 May 14;141(4):606-17. doi: 10.1016/j.cell.2010.04.026. Epub 2010 Apr 29.

Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.

Author information

  • 1Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. alwin.koehler@mfpl.ac.at

Abstract

Deubiquitinating enzymes (DUBs) regulate diverse cellular functions by cleaving ubiquitin from specific protein substrates. How their activities are modulated in various cellular contexts remains poorly understood. The yeast deubiquitinase Ubp8 protein is recruited and activated by the SAGA complex and, together with Sgf11, Sus1, and Sgf73, forms a DUB module responsible for deubiquitinating histone H2B during gene expression. Here, we report the crystal structure of the complete SAGA DUB module, which features two functional lobes structurally coupled by Sgf73. In the "assembly lobe," a long Sgf11 N-terminal helix is clamped onto the Ubp8 ZnF-UBP domain by Sus1. In the "catalytic lobe," an Sgf11 C-terminal zinc-finger domain binds to the Ubp8 catalytic domain next to its active site. Our structural and functional analyses reveal a central role of Sgf11 and Sgf73 in activating Ubp8 for deubiquitinating histone H2B and demonstrate how a DUB can be allosterically regulated by its nonsubstrate partners.

Copyright (c) 2010 Elsevier Inc. All rights reserved.

PMID:
20434206
[PubMed - indexed for MEDLINE]
PMCID:
PMC2901531
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

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

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