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Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination

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.


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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
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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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