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Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE.

Li X, Wang J, Shi Y
Nat Commun 2 408 (2011)
Related entries: 3sip, 3siq

Cited: 20 times
EuropePMC logo PMID: 21811237

Abstract

The Drosophila inhibitor of apoptosis protein DIAP1 exists in an auto-inhibited conformation, unable to suppress the effector caspase drICE. Auto-inhibition is disabled by caspase-mediated cleavage of DIAP1 after Asp20. The cleaved DIAP1 binds to mature drICE, inhibits its protease activity, and, presumably, also targets drICE for ubiquitylation. DIAP1-mediated suppression of drICE is effectively antagonized by the pro-apoptotic proteins Reaper, Hid, and Grim (RHG). Despite rigorous effort, the molecular mechanisms behind these observations are enigmatic. Here we report a 2.4 Å crystal structure of uncleaved DIAP1-BIR1, which reveals how the amino-terminal sequences recognize a conserved surface groove in BIR1 to achieve auto-inhibition, and a 3.5 Å crystal structure of active drICE bound to cleaved DIAP1-BIR1, which provides a structural explanation to DIAP1-mediated inhibition of drICE. These structures and associated biochemical analyses, together with published reports, define the molecular determinants that govern the interplay among DIAP1, drICE and the RHG proteins.

Reviews citing this publication (5)

  1. Developmentally programmed cell death in Drosophila. Denton D, Aung-Htut MT, Kumar S. Biochim Biophys Acta 1833 3499-3506 (2013)
  2. Regulation of Cell Death by IAPs and Their Antagonists. Vasudevan D, Ryoo HD. Curr Top Dev Biol 114 185-208 (2015)
  3. Physiological functions of non-apoptotic caspase activity in the nervous system. Hollville E, Deshmukh M. Semin Cell Dev Biol 82 127-136 (2018)
  4. Targeting intrinsic cell death pathways to control fungal pathogens. Kulkarni M, Stolp ZD, Hardwick JM. Biochem Pharmacol 162 71-78 (2019)
  5. Mechanisms Applied by Protein Inhibitors to Inhibit Cysteine Proteases. Tušar L, Usenik A, Turk B, Turk D. Int J Mol Sci 22 997 (2021)

Articles citing this publication (15)

  1. Regulation of Apoptosis by Inhibitors of Apoptosis (IAPs). Berthelet J, Dubrez L. Cells 2 163-187 (2013)
  2. In vivo CaspaseTracker biosensor system for detecting anastasis and non-apoptotic caspase activity. Tang HL, Tang HM, Fung MC, Hardwick JM. Sci Rep 5 9015 (2015)
  3. Crystal structure of the yeast metacaspase Yca1. Wong AH, Yan C, Shi Y. J Biol Chem 287 29251-29259 (2012)
  4. Multiple mechanisms modulate distinct cellular susceptibilities toward apoptosis in the developing Drosophila eye. Fan Y, Bergmann A. Dev Cell 30 48-60 (2014)
  5. Baculovirus Inhibitor-of-Apoptosis Op-IAP3 Blocks Apoptosis by Interaction with and Stabilization of a Host Insect Cellular IAP. Byers NM, Vandergaast RL, Friesen PD. J Virol 90 533-544 (2016)
  6. Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells. Zhang B, Xu Z, Zhang Y, Shao X, Xu X, Cheng J, Li Z. Pestic Biochem Physiol 119 81-89 (2015)
  7. Transcriptome analysis of Spodoptera frugiperda Sf9 cells reveals putative apoptosis-related genes and a preliminary apoptosis mechanism induced by azadirachtin. Shu B, Zhang J, Sethuraman V, Cui G, Yi X, Zhong G. Sci Rep 7 13231 (2017)
  8. A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis. Wang Z, Xia X, Yang X, Zhang X, Liu Y, Wu D, Fang Y, Liu Y, Xu J, Qiu Y, Zhou X. Elife 6 e30590 (2017)
  9. Detecting Anastasis In Vivo by CaspaseTracker Biosensor. Tang HM, Fung MC, Tang HL. J Vis Exp (2018)
  10. Detection of disordered regions in globular proteins using ¹³C-detected NMR. Gray FL, Murai MJ, Grembecka J, Cierpicki T. Protein Sci 21 1954-1960 (2012)
  11. Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates. Tuan VP, Yahara K, Dung HDQ, Binh TT, Huu Tung P, Tri TD, Thuan NPM, Khien VV, Trang TTH, Phuc BH, Tshibangu-Kabamba E, Matsumoto T, Akada J, Suzuki R, Okimoto T, Kodama M, Murakami K, Yano H, Fukuyo M, Takahashi N, Kato M, Nishiumi S, Azuma T, Ogura Y, Hayashi T, Toyoda A, Kobayashi I, Yamaoka Y. Microb Genom 7 (2021)
  12. In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila. Tang HL, Tang HM, Fung MC, Hardwick JM. J Vis Exp (2016)
  13. Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila. Wu Y, Lindblad JL, Garnett J, Kamber Kaya HE, Xu D, Zhao Y, Flores ER, Hardy J, Bergmann A. Cell Death Differ 23 723-732 (2016)
  14. Hunting for Cis-Regulatory Elements in Proteins. Gibson TJ, Kumar M. Cell Syst 2 68-70 (2016)
  15. A mathematical model for apoptotic switch in Drosophila. Ziraldo R, Ma L. Phys Biol 12 056003 (2015)


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