CIDE domains form functionally important higher-order assemblies for DNA fragmentation.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      DNA Fragmentation*; Deoxyribonucleases/*chemistry ; Poly-ADP-Ribose Binding Proteins/*chemistry ; Proteins/*chemistry; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/chemistry ; Binding Sites ; Cell Death ; Crystallography, X-Ray ; Drosophila Proteins/chemistry ; Drosophila melanogaster ; Homeostasis ; Lipids/chemistry ; Mice ; Microscopy, Electron, Transmission ; Molecular Conformation ; Mutation ; Protein Domains ; Protein Multimerization ; Proteins/genetics
    • Abstract:
      Cell death-inducing DFF45-like effector (CIDE) domains, initially identified in apoptotic nucleases, form a family with diverse functions ranging from cell death to lipid homeostasis. Here we show that the CIDE domains of Drosophila and human apoptotic nucleases Drep2, Drep4, and DFF40 all form head-to-tail helical filaments. Opposing positively and negatively charged interfaces mediate the helical structures, and mutations on these surfaces abolish nuclease activation for apoptotic DNA fragmentation. Conserved filamentous structures are observed in CIDE family members involved in lipid homeostasis, and mutations on the charged interfaces compromise lipid droplet fusion, suggesting that CIDE domains represent a scaffold for higher-order assembly in DNA fragmentation and other biological processes such as lipid homeostasis.
      Competing Interests: The authors declare no conflict of interest.
    • References:
      Apoptosis. 2014 Mar;19(3):428-35. (PMID: 24233238)
      Cell. 1999 Dec 23;99(7):747-55. (PMID: 10619428)
      Curr Biol. 1999 May 20;9(10):543-6. (PMID: 10339431)
      Cell. 2016 May 19;165(5):1055-66. (PMID: 27203110)
      Elife. 2014 Nov 13;3:null. (PMID: 25392983)
      J Biol Chem. 2000 Apr 28;275(17):12978-86. (PMID: 10777599)
      Cell. 2013 Apr 11;153(2):287-92. (PMID: 23582320)
      Biochem Biophys Res Commun. 2013 Oct 4;439(4):564-9. (PMID: 24025675)
      Nat Struct Biol. 2000 Aug;7(8):658-62. (PMID: 10932250)
      Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):10964-7. (PMID: 10500109)
      Mol Cell. 2004 May 21;14(4):531-9. (PMID: 15149602)
      Apoptosis. 2013 Apr;18(4):385-92. (PMID: 23417746)
      J Biol Chem. 2000 Jul 14;275(28):21402-8. (PMID: 10781612)
      J Biol Chem. 2016 Feb 26;291(9):4282-93. (PMID: 26733203)
      Nature. 1998 Jan 1;391(6662):96-9. (PMID: 9422513)
      Acta Crystallogr F Struct Biol Commun. 2014 Oct;70(Pt 10):1414-7. (PMID: 25286952)
      Nat Commun. 2013;4:1594. (PMID: 23481402)
      Cell. 1997 Apr 18;89(2):175-84. (PMID: 9108473)
      Methods Enzymol. 1997;276:307-26. (PMID: 27754618)
      Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702)
      EMBO J. 1998 May 1;17(9):2526-33. (PMID: 9564035)
      Arterioscler Thromb Vasc Biol. 2012 May;32(5):1094-8. (PMID: 22517368)
      Transl Androl Urol. 2016 Dec;5(6):935-950. (PMID: 28078226)
      Nature. 1998 Jan 1;391(6662):43-50. (PMID: 9422506)
      J Cell Biol. 1992 Nov;119(3):493-501. (PMID: 1400587)
      Cell Death Differ. 1999 Sep;6(9):823-4. (PMID: 10627165)
      Adv Exp Med Biol. 2016;924:47-51. (PMID: 27753018)
      Exp Cell Res. 2000 Apr 10;256(1):12-8. (PMID: 10739646)
      Proc Natl Acad Sci U S A. 2001 May 22;98(11):6051-5. (PMID: 11371636)
      Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32. (PMID: 15572765)
      J Biol Chem. 1999 May 14;274(20):13836-40. (PMID: 10318789)
      Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):352-7. (PMID: 20382987)
      FEBS Lett. 2012 Sep 21;586(19):3085-9. (PMID: 22850116)
    • Grant Information:
      DP1 HD087988 United States HD NICHD NIH HHS
    • Contributed Indexing:
      Keywords: CIDE family; DNA fragmentation; apoptosis; higher-order structure; lipid homeostasis
    • Molecular Sequence:
      PDB 4D2K; 5XPD; 5XPC
    • Accession Number:
      0 (Apoptosis Regulatory Proteins)
      0 (Drep2 protein, Drosophila)
      0 (Drosophila Proteins)
      0 (Lipids)
      0 (Poly-ADP-Ribose Binding Proteins)
      0 (Proteins)
      0 (caspase-activated DNase inhibitor)
      EC 3.1.- (DFFB protein, human)
      EC 3.1.- (Deoxyribonucleases)
      EC 3.1.- (Drep4 protein, Drosophila)
      EC 3.1.- (caspase-activated deoxyribonuclease)
    • Publication Date:
      Date Created: 20170628 Date Completed: 20180601 Latest Revision: 20210726
    • Publication Date:
      20221213
    • Accession Number:
      PMC5514754
    • Accession Number:
      10.1073/pnas.1705949114
    • Accession Number:
      28652364