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- Title
Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination.
- Authors
Chai, Jijie; Yan, Nieng; Huh, Jun R; Wu, Jia-Wei; Li, Wenyu; Hay, Bruce A; Shi, Yigong
- Abstract
The inhibitor of apoptosis protein DIAP1 inhibits Dronc-dependent cell death by ubiquitinating Dronc. The pro-death proteins Reaper, Hid and Grim (RHG) promote apoptosis by antagonizing DIAP1 function. Here we report the structural basis of Dronc recognition by DIAP1 as well as a novel mechanism by which the RHG proteins remove DIAP1-mediated downregulation of Dronc. Biochemical and structural analyses revealed that the second BIR (BIR2) domain of DIAP1 recognizes a 12-residue sequence in Dronc. This recognition is essential for DIAP1 binding to Dronc, and for targeting Dronc for ubiquitination. Notably, the Dronc-binding surface on BIR2 coincides with that required for binding to the N termini of the RHG proteins, which competitively eliminate DIAP1-mediated ubiquitination of Dronc. These observations reveal the molecular mechanisms of how DIAP1 recognizes Dronc, and more importantly, how the RHG proteins remove DIAP1-mediated ubiquitination of Dronc.
- Subjects
CYSTEINE proteinases; APOPTOSIS; PROTEINASES; CELL death; PROTEINS
- Publication
Nature Structural Biology, 2003, Vol 10, Issue 11, p892
- ISSN
1072-8368
- Publication type
Article
- DOI
10.1038/nsb989