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PDBsum entry 1jd5

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Apoptosis PDB id
1jd5
Jmol
Contents
Protein chain
105 a.a. *
Ligands
ALA-ILE-ALA-TYR-
PHE-ILE-PRO-ASP
Metals
_ZN
* Residue conservation analysis
PDB id:
1jd5
Name: Apoptosis
Title: Crystal structure of diap1-bir2/grim
Structure: Apoptosis 1 inhibitor. Chain: a. Synonym: diap1. Engineered: yes. Cell death protein grim. Chain: b. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: diap1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence is naturally found in drosophila melanogaster
Biol. unit: Tetramer (from PQS)
Resolution:
1.90Å     R-factor:   0.202     R-free:   0.243
Authors: J.W.Wu,A.E.Cocina,J.Chai,B.A.Hay,Y.Shi
Key ref:
J.W.Wu et al. (2001). Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol Cell, 8, 95. PubMed id: 11511363 DOI: 10.1016/S1097-2765(01)00282-9
Date:
12-Jun-01     Release date:   05-Dec-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q24306  (IAP1_DROME) -  Apoptosis 1 inhibitor
Seq:
Struc:
438 a.a.
105 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S1097-2765(01)00282-9 Mol Cell 8:95 (2001)
PubMed id: 11511363  
 
 
Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.
J.W.Wu, A.E.Cocina, J.Chai, B.A.Hay, Y.Shi.
 
  ABSTRACT  
 
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 alpha 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.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall Structure of the DIAP1-BIR2 Domain by Itself (A) and in Complex with the Grim (B) or Hid (C) PeptideThe DIAP1-BIR2 domain is shown in cyan and the bound Grim and Hid peptides are highlighted in orange and pink, respectively. The zinc atom in the BIR domain is colored red, while its coordinating residues are shown in yellow. Some of the secondary structural elements are labeled. In (D), the structures of DIAP1-BIR2 by itself and in complex with the Hid/Grim peptides are superimposed with that of XIAP-BIR3 in complex with the Smac tetrapeptide (Protein Data Bank code 1G73). The DIAP1-BIR2 and XIAP-BIR3 are shown in cyan and purple, respectively. The bound Grim and Hid peptides are highlighted in orange and pink, respectively, while the Smac tetrapeptide is represented in green. Helix α6, highlighted in red, is only present in the peptide-bound BIR2
Figure 4.
Figure 4. Specific Recognition of DIAP1-BIR2 by the Hid and Grim Peptides(A) Stereo view of the interface between DIAP1-BIR2, colored cyan, and the bound Grim peptide, in orange. The important residues in DIAP1 are highlighted in yellow. Hydrogen bonds are represented by red dashed lines. The same DIAP1-BIR2 orientation is maintained for (C).(B) Close up view of the hydrophobic interface between DIAP1-BIR2 and the Grim peptide. The coloring scheme is the same as in (A).(C) Stereo view of the interface between DIAP1-BIR2 and the bound Hid peptide, shown in pink
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 95-0) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21220123 S.Yuan, X.Yu, M.Topf, L.Dorstyn, S.Kumar, S.J.Ludtke, and C.W.Akey (2011).
Structure of the Drosophila apoptosome at 6.9 å resolution.
  Structure, 19, 128-140.
PDB codes: 1vt4 3iz8
20837774 C.Sandu, H.D.Ryoo, and H.Steller (2010).
Drosophila IAP antagonists form multimeric complexes to promote cell death.
  J Cell Biol, 190, 1039-1052.  
19373243 P.D.Mace, S.Shirley, and C.L.Day (2010).
Assembling the building blocks: structure and function of inhibitor of apoptosis proteins.
  Cell Death Differ, 17, 46-53.  
19212814 D.M.Cooper, D.J.Granville, and C.Lowenberger (2009).
The insect caspases.
  Apoptosis, 14, 247-256.  
19737742 M.Mallik, and S.C.Lakhotia (2009).
The developmentally active and stress-inducible noncoding hsromega gene is a novel regulator of apoptosis in Drosophila.
  Genetics, 183, 831-852.  
19495985 M.Orme, and P.Meier (2009).
Inhibitor of apoptosis proteins in Drosophila: gatekeepers of death.
  Apoptosis, 14, 950-960.  
18239672 B.P.Eckelman, M.Drag, S.J.Snipas, and G.S.Salvesen (2008).
The mechanism of peptide-binding specificity of IAP BIR domains.
  Cell Death Differ, 15, 920-928.  
19026784 M.Ditzel, M.Broemer, T.Tenev, C.Bolduc, T.V.Lee, K.T.Rigbolt, R.Elliott, M.Zvelebil, B.Blagoev, A.Bergmann, and P.Meier (2008).
Inactivation of effector caspases through nondegradative polyubiquitylation.
  Mol Cell, 32, 540-553.  
18854135 M.X.O'Riordan, L.D.Bauler, F.L.Scott, and C.S.Duckett (2008).
Inhibitor of apoptosis proteins in eukaryotic evolution and development: a model of thematic conservation.
  Dev Cell, 15, 497-508.  
16794601 A.M.Verhagen, T.K.Kratina, C.J.Hawkins, J.Silke, P.G.Ekert, and D.L.Vaux (2007).
Identification of mammalian mitochondrial proteins that interact with IAPs via N-terminal IAP binding motifs.
  Cell Death Differ, 14, 348-357.  
17068333 J.R.Huh, I.Foe, I.Muro, C.H.Chen, J.H.Seol, S.J.Yoo, M.Guo, J.M.Park, and B.A.Hay (2007).
The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival, required for the innate immune response to gram-negative bacterial infection, and can be negatively regulated by the reaper/hid/grim family of IAP-binding apoptosis inducers.
  J Biol Chem, 282, 2056-2068.  
17557079 M.Challa, S.Malladi, B.J.Pellock, D.Dresnek, S.Varadarajan, Y.W.Yin, K.White, and S.B.Bratton (2007).
Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease.
  EMBO J, 26, 3144-3156.  
18166655 P.S.Ribeiro, E.Kuranaga, T.Tenev, F.Leulier, M.Miura, and P.Meier (2007).
DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells.
  J Cell Biol, 179, 1467-1480.  
17205079 Y.Herman-Bachinsky, H.D.Ryoo, A.Ciechanover, and H.Gonen (2007).
Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several distinct ubiquitin system pathways.
  Cell Death Differ, 14, 861-871.  
16842034 B.A.Hay, and M.Guo (2006).
Caspase-dependent cell death in Drosophila.
  Annu Rev Cell Dev Biol, 22, 623-650.  
16200201 C.W.Wright, and C.S.Duckett (2005).
Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function.
  J Clin Invest, 115, 2673-2678.  
16041319 L.Zhou, G.Jiang, G.Chan, C.P.Santos, D.W.Severson, and L.Xiao (2005).
Michelob_x is the missing inhibitor of apoptosis protein antagonist in mosquito genomes.
  EMBO Rep, 6, 769-774.  
15905883 L.Zhou (2005).
The 'unique key' feature of the Iap-binding motifs in RHG proteins.
  Cell Death Differ, 12, 1148-1151.  
16212486 N.Yan, and Y.Shi (2005).
Mechanisms of apoptosis through structural biology.
  Annu Rev Cell Dev Biol, 21, 35-56.  
15681434 Q.Li, P.Liston, and R.W.Moyer (2005).
Functional analysis of the inhibitor of apoptosis (iap) gene carried by the entomopoxvirus of Amsacta moorei.
  J Virol, 79, 2335-2345.  
15580265 T.Tenev, A.Zachariou, R.Wilson, M.Ditzel, and P.Meier (2005).
IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms.
  Nat Cell Biol, 7, 70-77.  
15268856 J.R.Huh, M.Guo, and B.A.Hay (2004).
Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role.
  Curr Biol, 14, 1262-1266.  
15107838 N.Yan, J.W.Wu, J.Chai, W.Li, and Y.Shi (2004).
Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim.
  Nat Struct Mol Biol, 11, 420-428.
PDB codes: 1sdz 1se0
15520809 S.J.Riedl, and Y.Shi (2004).
Molecular mechanisms of caspase regulation during apoptosis.
  Nat Rev Mol Cell Biol, 5, 897-907.  
15150408 V.P.Yin, and C.S.Thummel (2004).
A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila.
  Proc Natl Acad Sci U S A, 101, 8022-8027.  
14517550 J.Chai, N.Yan, J.R.Huh, J.W.Wu, W.Li, B.A.Hay, and Y.Shi (2003).
Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination.
  Nat Struct Biol, 10, 892-898.
PDB code: 1q4q
12456331 L.Zhou, R.Yuan, and L.Serggio (2003).
Molecular mechanisms of irradiation-induced apoptosis.
  Front Biosci, 8, d9-19.  
12446669 M.R.Olson, C.L.Holley, S.J.Yoo, J.R.Huh, B.A.Hay, and S.Kornbluth (2003).
Reaper is regulated by IAP-mediated ubiquitination.
  J Biol Chem, 278, 4028-4034.  
11818065 A.Christich, S.Kauppila, P.Chen, N.Sogame, S.I.Ho, and J.M.Abrams (2002).
The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid.
  Curr Biol, 12, 137-140.  
11980716 A.Rodriguez, P.Chen, H.Oliver, and J.M.Abrams (2002).
Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf-1 homolog, Dark.
  EMBO J, 21, 2189-2197.  
12021770 C.L.Holley, M.R.Olson, D.A.Colón-Ramos, and S.Kornbluth (2002).
Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.
  Nat Cell Biol, 4, 439-444.  
12042762 G.S.Salvesen, and C.S.Duckett (2002).
IAP proteins: blocking the road to death's door.
  Nat Rev Mol Cell Biol, 3, 401-410.  
12021769 H.D.Ryoo, A.Bergmann, H.Gonen, A.Ciechanover, and H.Steller (2002).
Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1.
  Nat Cell Biol, 4, 432-438.  
11971981 H.Okada, W.K.Suh, J.Jin, M.Woo, C.Du, A.Elia, G.S.Duncan, A.Wakeham, A.Itie, S.W.Lowe, X.Wang, and T.W.Mak (2002).
Generation and characterization of Smac/DIABLO-deficient mice.
  Mol Cell Biol, 22, 3509-3517.  
11818064 J.P.Wing, J.S.Karres, J.L.Ogdahl, L.Zhou, L.M.Schwartz, and J.R.Nambu (2002).
Drosophila sickle is a novel grim-reaper cell death activator.
  Curr Biol, 12, 131-135.  
12427028 L.E.Luque, K.P.Grape, and M.Junker (2002).
A highly conserved arginine is critical for the functional folding of inhibitor of apoptosis (IAP) BIR domains.
  Biochemistry, 41, 13663-13671.  
12021767 S.J.Yoo, J.R.Huh, I.Muro, H.Yu, L.Wang, S.L.Wang, R.M.Feldman, R.J.Clem, H.A.Müller, and B.A.Hay (2002).
Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms.
  Nat Cell Biol, 4, 416-424.  
11818063 S.M.Srinivasula, P.Datta, M.Kobayashi, J.W.Wu, M.Fujioka, R.Hegde, Z.Zhang, R.Mukattash, T.Fernandes-Alnemri, Y.Shi, J.B.Jaynes, and E.S.Alnemri (2002).
sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein.
  Curr Biol, 12, 125-130.  
12356728 T.Tenev, A.Zachariou, R.Wilson, A.Paul, and P.Meier (2002).
Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1.
  EMBO J, 21, 5118-5129.  
11931755 Y.Shi (2002).
Mechanisms of caspase activation and inhibition during apoptosis.
  Mol Cell, 9, 459-470.  
12401491 Z.Huang (2002).
The chemical biology of apoptosis. Exploring protein-protein interactions and the life and death of cells with small molecules.
  Chem Biol, 9, 1059-1072.  
11711663 S.W.Fesik, and Y.Shi (2001).
Structural biology. Controlling the caspases.
  Science, 294, 1477-1478.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.