Modeling the zing finger protein SmZF1 from Schistosoma mansoni: Insights into DNA binding and gene regulation

Bitar, Mainá; Drummond, Marcela Gonçalves; Costa, Maurício G. S.; Lobo, Francisco Pereira; Calzavara-Silva, Carlos Eduardo; Bisch, Paulo Mascarello; Machado, Carlos Renato; Macedo, Andréa Mara; Pierce, Raymond J.; Franco, Glória Regina

doi:10.1016/j.jmgm.2012.10.004

Cited by 5 publications

(3 citation statements)

References 68 publications

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“…Zinc finger motifs are relatively small protein motifs that fold around one or more zinc ions and are widely found in eukaryotes. Many zinc finger proteins are DNA-binding proteins involved in the regulation of gene expression [48]. In addition to their role as a DNA-binding motif, zinc finger motifs have been shown to mediate protein–protein or protein–lipid interactions [49], [50].…”

Section: Discussionmentioning

confidence: 99%

Protein N-Myristoylation Plays a Critical Role in the Endoplasmic Reticulum Morphological Change Induced by Overexpression of Protein Lunapark, an Integral Membrane Protein of the Endoplasmic Reticulum

et al. 2013

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N-myristoylation of eukaryotic cellular proteins has been recognized as a modification that occurs mainly on cytoplasmic proteins. In this study, we examined the membrane localization, membrane integration, and intracellular localization of four recently identified human N-myristoylated proteins with predicted transmembrane domains. As a result, it was found that protein Lunapark, the human ortholog of yeast protein Lnp1p that has recently been found to be involved in network formation of the endoplasmic reticulum (ER), is an N-myristoylated polytopic integral membrane protein. Analysis of tumor necrosis factor-fusion proteins with each of the two putative transmembrane domains and their flanking regions of protein Lunapark revealed that transmembrane domain 1 and 2 functioned as type II signal anchor sequence and stop transfer sequence, respectively, and together generated a double-spanning integral membrane protein with an N-/C-terminal cytoplasmic orientation. Immunofluorescence staining of HEK293T cells transfected with a cDNA encoding protein Lunapark tagged with FLAG-tag at its C-terminus revealed that overexpressed protein Lunapark localized mainly to the peripheral ER and induced the formation of large polygonal tubular structures. Morphological changes in the ER induced by overexpressed protein Lunapark were significantly inhibited by the inhibition of protein N-myristoylation by means of replacing Gly2 with Ala. These results indicated that protein N-myristoylation plays a critical role in the ER morphological change induced by overexpression of protein Lunapark.

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Section: Discussionmentioning

confidence: 99%

Protein N-Myristoylation Plays a Critical Role in the Endoplasmic Reticulum Morphological Change Induced by Overexpression of Protein Lunapark, an Integral Membrane Protein of the Endoplasmic Reticulum

et al. 2013

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“…Boltzmannian stochastics have also been used to calculate populations of 3D structures of CPPs using PepLook, calculating both intra- and intermolecular interactions [15]. Molecular dynamics simulations have also been carried out on penetratin and the TAT peptide with lipid bilayers [16–18], as well as of dimer peptides [19] or zinc-fingers [20] with DNA, and the CPP CADY in complex with siRNA [21]. Molecular modeling can also discover ligands to nucleic acids [22].…”

Section: Introductionmentioning

confidence: 99%

Peptide-Ligand Binding Modeling of siRNA with Cell-Penetrating Peptides

García-Sosa

Tulp

Langel

et al. 2014

BioMed Research International

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The binding affinity of a series of cell-penetrating peptides (CPP) was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides' ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA.

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“…Due to its complex life cycle, the parasite can be considered as a challenging biological system to study regulation of gene expression (El-Ansary and Al- Daihan, 2005;Jolly et al 2007;Fantappie et al 2008). Thus, characterization of the proteins involved in the control of gene expression is of utmost importance and this is corroborated by the growing number of publications in this field (Lu et al 2006;Wu et al 2007Drummond et al 2009;Bitar et al 2012). Also, the functional characterization of these proteins could lead to the identification of new potential drug targets in the parasite.…”

mentioning

confidence: 99%

Identification of a newSchistosoma mansoniSMYB1 partner: putative roles in RNA metabolism

Rocha¹,

Valadão²,

Rezende³

et al. 2013

Parasitology

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SMYB1 is a Schistosoma mansoni protein highly similar to members of the Y-box binding protein family. Similar to other homologues, SMYB1 is able to bind double- and single-stranded DNA, as well as RNA molecules. The characterization of proteins involved in the regulation of gene expression in S. mansoni is of great importance for the understanding of molecular events that control morphological and physiological changes in this parasite. Here we demonstrate that SMYB1 is located in the cytoplasm of cells from different life-cycle stages of S. mansoni, suggesting that this protein is probably acting in mRNA metabolism in the cytoplasm and corroborating previous findings from our group that showed its ability to bind RNA. Protein-protein interactions are important events in all biological processes, since most proteins execute their functions through large supramolecular structures. Yeast two-hybrid screenings using SMYB1 as bait identified a partner in S. mansoni similar to the SmD3 protein of Drosophila melanogaster (SmRNP), which is important in the assembly of small nuclear ribonucleoprotein complexes. Also, pull-down assays were conducted using immobilized GST-SMYB1 proteins and confirmed the SMYB1-SmRNP interaction. The interaction of SMYB1 with a protein involved in mRNA processing suggests that it may act in processes such as turnover, transport and stabilization of RNA molecules.

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Modeling the zing finger protein SmZF1 from Schistosoma mansoni: Insights into DNA binding and gene regulation

Cited by 5 publications

References 68 publications

Protein N-Myristoylation Plays a Critical Role in the Endoplasmic Reticulum Morphological Change Induced by Overexpression of Protein Lunapark, an Integral Membrane Protein of the Endoplasmic Reticulum

Protein N-Myristoylation Plays a Critical Role in the Endoplasmic Reticulum Morphological Change Induced by Overexpression of Protein Lunapark, an Integral Membrane Protein of the Endoplasmic Reticulum

Peptide-Ligand Binding Modeling of siRNA with Cell-Penetrating Peptides

Identification of a newSchistosoma mansoniSMYB1 partner: putative roles in RNA metabolism

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