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Structural Analysis of a Functional DIAP1 Fragment Bound to Grim and Hid Peptides

Wu, Jia-Wei and Cocina, Amy E. and Chai, Jijie and Hay, Bruce A. and Shi, Yigong (2001) Structural Analysis of a Functional DIAP1 Fragment Bound to Grim and Hid Peptides. Molecular Cell, 8 (1). pp. 95-104. ISSN 1097-2765. doi:10.1016/s1097-2765(01)00282-9.

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The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional α helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.

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Additional Information:© 2001 Cell Press. Received 20 April 2001, Accepted 15 May 2001, Available online 20 August 2001. We thank F. Hughson for critical reading of the manuscript, S. Kyin for peptide synthesis/sequencing and mass spectroscopy; and N. Hunt for secretarial assistance. This research is supported by start-up funds from Princeton University (Y.S.) and NIH grants (CA90269 to Y.S.). Y.S. is a Searle Scholar and a Rita Allen Scholar. Accession Numbers: Protein Data Bank codes for DIAP1-BIR2 by itself and in complex with Grim and Hid peptides are 1JD4, 1JD5, and 1JD6, respectively.
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Princeton UniversityUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
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Record Number:CaltechAUTHORS:20200428-141620198
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Official Citation:Jia-Wei Wu, Amy E. Cocina, Jijie Chai, Bruce A. Hay, Yigong Shi, Structural Analysis of a Functional DIAP1 Fragment Bound to Grim and Hid Peptides, Molecular Cell, Volume 8, Issue 1, 2001, Pages 95-104, ISSN 1097-2765, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102886
Deposited By: Tony Diaz
Deposited On:28 Apr 2020 21:52
Last Modified:16 Nov 2021 18:16

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