The Crystal Structure of the C-Terminal DAP5/p97 Domain Sheds Light on the Molecular Basis for Its Processing by Caspase Cleavage

Liberman, Noa; Dym, Orly; Unger, Tamar; Albeck, Shira; Peleg, Yoav; Jacobovitch, Yossi; Branzburg, Anna; Eisenstein, Miriam; Marash, Lea; Kimchi, Adi

doi:10.1016/j.jmb.2008.08.013

Cited by 14 publications

(22 citation statements)

References 49 publications

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“…SS1G_13235 has analogy to the C-terminal domain of death-associated protein 5 (DAP5), a member of the eukaryotic translation initiation factor eIF4G protein family (Figure 6c). Cleavage of DAP5 by caspases at its C-terminus induces apoptosis [58]. SS1G_07354 also had eIF4G protein as closest analog (Table 4).…”

Section: Resultsmentioning

confidence: 99%

Secretome analysis reveals effector candidates associated with broad host range necrotrophy in the fungal plant pathogen Sclerotinia sclerotiorum

et al. 2014

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BackgroundThe white mold fungus Sclerotinia sclerotiorum is a devastating necrotrophic plant pathogen with a remarkably broad host range. The interaction of necrotrophs with their hosts is more complex than initially thought, and still poorly understood.ResultsWe combined bioinformatics approaches to determine the repertoire of S. sclerotiorum effector candidates and conducted detailed sequence and expression analyses on selected candidates. We identified 486 S. sclerotiorum secreted protein genes expressed in planta, many of which have no predicted enzymatic activity and may be involved in the interaction between the fungus and its hosts. We focused on those showing (i) protein domains and motifs found in known fungal effectors, (ii) signatures of positive selection, (iii) recent gene duplication, or (iv) being S. sclerotiorum-specific. We identified 78 effector candidates based on these properties. We analyzed the expression pattern of 16 representative effector candidate genes on four host plants and revealed diverse expression patterns.ConclusionsThese results reveal diverse predicted functions and expression patterns in the repertoire of S. sclerotiorum effector candidates. They will facilitate the functional analysis of fungal pathogenicity determinants and should prove useful in the search for plant quantitative disease resistance components active against the white mold.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-336) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Secretome analysis reveals effector candidates associated with broad host range necrotrophy in the fungal plant pathogen Sclerotinia sclerotiorum

et al. 2014

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“…1A) resemble the 2 conserved aromatic and acidic boxes previously observed within the W2 domain of mammalian eIF4G and related proteins. 25,43 It is likely then that both MA3 and W2 domains, divergent in sequence due to the greater evolutionary distance between trypanosomatids and higher eukaryotes, are present in the EIF4G3 and EIF4G4 homologues.…”

Section: Resultsmentioning

confidence: 99%

Two related trypanosomatid eIF4G homologues have functional differences compatible with distinct roles during translation initiation

et al. 2015

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Abbreviations: eIF, eukaryotic Initiation Factor, PABP, Poly(A) Binding Protein, MIF4G, Middle domain of eukaryotic Initiation Factor 4G, HEAT domain, Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A) and the yeast kinase TOR1, GST, Glutathione-S-TransferaseIn higher eukaryotes, eIF4A, eIF4E and eIF4G homologues interact to enable mRNA recruitment to the ribosome. eIF4G acts as a scaffold for these interactions and also interacts with other proteins of the translational machinery. Trypanosomatid protozoa have multiple homologues of eIF4E and eIF4G and the precise function of each remains unclear. Here, 2 previously described eIF4G homologues, EIF4G3 and EIF4G4, were further investigated. In vitro, both homologues bound EIF4AI, but with different interaction properties. Binding to distinct eIF4Es was also confirmed; EIF4G3 bound EIF4E4 while EIF4G4 bound EIF4E3, both these interactions required similar binding motifs. EIF4G3, but not EIF4G4, interacted with PABP1, a poly-A binding protein homolog. Work in vivo with Trypanosoma brucei showed that both EIF4G3 and EIF4G4 are cytoplasmic and essential for viability. Depletion of EIF4G3 caused a rapid reduction in total translation while EIF4G4 depletion led to changes in morphology but no substantial inhibition of translation. Sitedirected mutagenesis was used to disrupt interactions of the eIF4Gs with either eIF4E or eIF4A, causing different levels of growth inhibition. Overall the results show that only EIF4G3, with its cap binding partner EIF4E4, plays a major role in translational initiation.

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“…Thus, p97/NAT1/DAP5 is a macromolecular mimic of the eIF4G C-terminal half (12,13), and it has been implicated in the modulation of translation for specific mRNAs (14). Interestingly the DAP5-CTD 3D structure is very similar to that of the W2-CTDs of eIF5 and eIF2Bε, and in common with these factors, but unlike eIF4G, DAP5 also binds to eIF2β (15). …”

Section: Introductionmentioning

confidence: 91%

Mechanisms of translational regulation by a human eIF5-mimic protein

Singh

Watanabe

Zhou

et al. 2011

Nucleic Acids Research

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The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNAiMet ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2Bε or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function.

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The Crystal Structure of the C-Terminal DAP5/p97 Domain Sheds Light on the Molecular Basis for Its Processing by Caspase Cleavage

Cited by 14 publications

References 49 publications

Secretome analysis reveals effector candidates associated with broad host range necrotrophy in the fungal plant pathogen Sclerotinia sclerotiorum

Secretome analysis reveals effector candidates associated with broad host range necrotrophy in the fungal plant pathogen Sclerotinia sclerotiorum

Two related trypanosomatid eIF4G homologues have functional differences compatible with distinct roles during translation initiation

Mechanisms of translational regulation by a human eIF5-mimic protein

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