Ddi1, a Eukaryotic Protein With the Retroviral Protease Fold

Sirkis, Roy; Gerst, Jeffrey E.; Fass, Deborah

doi:10.1016/j.jmb.2006.08.086

Cited by 79 publications

(130 citation statements)

References 59 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…This finding can probably be extrapolated to the other proteins from this family that has an RP domain. Using molecular modeling, this study shows that there is a high degree of structural homology between the RP domains of the L. major Ddi1-like protein and that of the orthologous enzyme in S. cerevisiae (Sirkis et al 2006). The RP domain of the parasite protein, just as with that from S. cerevisiae, folds to give rise to a homodimer which is characteristic of the A 2 aspartyl proteinases, in which each monomer provides one aspartic acid associated with the catalytic mechanism.…”

Section: Discussionmentioning

confidence: 91%

“…A 3D model of the dimerized RP domain of the L. major Ddi1-like protein was generated using homology modeling procedures and the coordinates of the dimerized RP domain of yeast Ddi1 (PDB ID: 2I1A; Sirkis et al 2006) as a template. The sequence identity between the sequences was 45 % (length of aligned domain, 127 amino acids).…”

Section: Bioinformatics and Modeling Proceduresmentioning

confidence: 99%

“…AAALLFDT Structural model of the RP domain of the L. major Ddi1-like protein A 3D model for the RP domain of the L. major Ddi1-like protein was generated using homology modeling procedures based on sequence comparison between this protein and its close crystallized homolog, the dimerized RP domain of Saccharomyces Ddi1 (PDB ID: 2I1A; Sirkis et al 2006). The modeled dimer (Fig.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

See 2 more Smart Citations

Ddi1-like protein from Leishmania major is an active aspartyl proteinase

Perteguer

Gómez‐Puertas

Cañavate

et al. 2013

Cell Stress and Chaperones

View full text Add to dashboard Cite

Eukaryotic cells respond to DNA damage by activating damage checkpoint pathways, which arrest cell cycle progression and induce gene expression. We isolated a full-length cDNA encoding a 49-kDa protein from Leishmania major, which exhibited significant deduced amino acid sequence homology with the annotated Leishmania sp. DNA damage-inducible (Ddi1-like) protein, as well as with the Ddi1 protein from Saccharomyces cerevisiae. In contrast to the previously described Ddi1 protein, the protein from L. major displays three domains: (1) an NH2-terminal ubiquitin like; (2) a COOH terminal ubiquitinassociated; (3) a retroviral aspartyl proteinase, containing the typical D[S/T]G signature. The function of the L. major Ddi1-like recombinant protein was investigated after expression in baculovirus/insect cells and biochemical analysis, revealing preferential substrate selectivity for aspartyl proteinase A 2 family substrates, with optimal activity in acidic conditions. The proteolytic activity was inhibited by aspartyl proteinase inhibitors. Molecular modeling of the retroviral domain of the Ddi1-like Leishmania protein revealed a dimer structure that contained a double AspSer-Gly-Ala amino acid sequence motif, in an almost identical geometry to the exhibited by the homologous retroviral aspartyl protease domain of yeast Ddi1 protein. Our results indicate that the isolated Ddi1-like protein is a functional aspartyl proteinase in L. major, opening possibility to be considered as a potential target for novel antiparasitic drugs.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Bioinformatics and Modeling Proceduresmentioning

confidence: 99%

Section: ------------------------------------------------------------mentioning

confidence: 99%

See 1 more Smart Citation

Ddi1-like protein from Leishmania major is an active aspartyl proteinase

Perteguer

Gómez‐Puertas

Cañavate

et al. 2013

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…Ddi1, for example, contains an aspartyl protease domain that is likely to be functional based on its crystal structure and on the identification of a defined phenotype in an active-site substitution mutant (Sirkis et al 2006;White et al 2011). Thus, the protease activity of Ddi1 could possibly provide an alternative to the proteasome as a means to attack ubiquitylated proteins.…”

Section: Regulatory Particlementioning

confidence: 99%

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

et al. 2012

View full text Add to dashboard Cite

Protein modifications provide cells with exquisite temporal and spatial control of protein function. Ubiquitin is among the most important modifiers, serving both to target hundreds of proteins for rapid degradation by the proteasome, and as a dynamic signaling agent that regulates the function of covalently bound proteins. The diverse effects of ubiquitylation reflect the assembly of structurally distinct ubiquitin chains on target proteins. The resulting ubiquitin code is interpreted by an extensive family of ubiquitin receptors. Here we review the components of this regulatory network and its effects throughout the cell.

show abstract

“…Therefore, the founder of the EP (LTR) retrotransposon branch most likely evolved through recombination between a TP (non-LTR) retrotransposon and a DNA transposon (115,116). The aspartic protease of the EP retroelements is homologous to the pan-eukaryotic protein DDI1, an essential, ubiquitin-dependent regulator of the cell cycle, and DDI1, in turn, appears to have been derived from a distinct group of bacterial aspartyl proteases (117,118). Thus, strikingly, the ancestral Pol polyprotein of the EP retroelements seems to have been assembled from four distinct components, only one of which, the RT, is derived from a preexisting retroelement.…”

Section: Retroelements and Retroviruses: Viruses As Derived Formsmentioning

confidence: 99%

Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements

Koonin

Dolja

2014

Microbiol Mol Biol Rev

215

211

View full text Add to dashboard Cite

SUMMARY Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms. Structurally similar, apparently homologous capsids are present in a huge variety of icosahedral viruses that infect bacteria, archaea, and eukaryotes. These findings prompted the concept of the capsid as the virus “self” that defines the identity of deep, ancient viral lineages. However, several other widespread viral “hallmark genes” encode key components of the viral replication apparatus (such as polymerases and helicases) and combine with different capsid proteins, given the inherently modular character of viral evolution. Furthermore, diverse, widespread, capsidless selfish genetic elements, such as plasmids and various types of transposons, share hallmark genes with viruses. Viruses appear to have evolved from capsidless selfish elements, and vice versa, on multiple occasions during evolution. At the earliest, precellular stage of life's evolution, capsidless genetic parasites most likely emerged first and subsequently gave rise to different classes of viruses. In this review, we develop the concept of a greater virus world which forms an evolutionary network that is held together by shared conserved genes and includes both bona fide capsid-encoding viruses and different classes of capsidless replicons. Theoretical studies indicate that selfish replicons (genetic parasites) inevitably emerge in any sufficiently complex evolving ensemble of replicators. Therefore, the key signature of the greater virus world is not the presence of a capsid but rather genetic, informational parasitism itself, i.e., various degrees of reliance on the information processing systems of the host.

show abstract

Ddi1, a Eukaryotic Protein With the Retroviral Protease Fold

Cited by 79 publications

References 59 publications

Ddi1-like protein from Leishmania major is an active aspartyl proteinase

Ddi1-like protein from Leishmania major is an active aspartyl proteinase

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements

Contact Info

Product

Resources

About