Chai, Jijie and Yan, Nieng and Huh, Jun R. and Wu, Jia-Wei and Li, Wenyu and Hay, Bruce A. and Shi, Yigong (2003) Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nature Structural Biology, 10 (11). pp. 892-898. ISSN 1072-8368. doi:10.1038/nsb989. https://resolver.caltech.edu/CaltechAUTHORS:20150407-132124732
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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.
Item Type: | Article | |||||||||
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Additional Information: | © 2003 Nature Publishing Group. Received 26 June 2003; Accepted 13 August 2003; Published online: 28 September 2003. We thank L. Walsh and others at CHESS for help with beam time and data collection. This research was supported by US National Institutes of Health grants. | |||||||||
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Issue or Number: | 11 | |||||||||
DOI: | 10.1038/nsb989 | |||||||||
Record Number: | CaltechAUTHORS:20150407-132124732 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20150407-132124732 | |||||||||
Official Citation: | Chai, J., Yan, N., Huh, J. et al. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Mol Biol 10, 892–898 (2003). https://doi.org/10.1038/nsb989 | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 56437 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | Ruth Sustaita | |||||||||
Deposited On: | 07 Apr 2015 20:59 | |||||||||
Last Modified: | 10 Nov 2021 20:59 |
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