References of "Charloteaux, Benoît"
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See detailCombined use of GWAS and eQTL information to identify genes controlling platelet biology
Gori, Ann-Stephan ULg; LECUT, Christelle ULg; Theatre, Emilie ULg et al

Poster (2014, April 24)

Genome Wide Association Studies (GWAS) have identified at least 68 loci involved in megakaryopoiesis and platelet formation. As for all GWAS, identified risk loci span hundreds of kilobases encompassing ... [more ▼]

Genome Wide Association Studies (GWAS) have identified at least 68 loci involved in megakaryopoiesis and platelet formation. As for all GWAS, identified risk loci span hundreds of kilobases encompassing multiple genes, such that causative variants and genes remain largely unknown. To aid in the identification of causative genes underlying GWAS hits for platelet function (as well as other phenotypes including common complex diseases), we have generated a dataset (" CEDAR ") comprising genome-wide SNP and transcriptome data on nine primary cell types, including platelets, for 330 healthy Caucasian individuals. In addition, we have measured platelet counts and volume, as well as platelet reactivity to ADP, collagen and thrombin-related peptide for all these individuals. After extensive quality control, the ensuing data set has been used to identify (i) QTL influencing platelet count, volume and reactivity, and (ii) cis-and transacting eQTL operating in platelets. To aid in the identification of genes underlying platelet biology, we are applying a recently developed method to search for correlations between association patterns with platelet phenotypes and eQTL association patterns. Such findings would strongly incriminate the corresponding genes (affected by the eQTL) as being causally involved in determining the cognate platelet phenotype. Latest results will be presented. [less ▲]

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See detailA proteome-scale map of the human interactome network.
Rolland, Thomas; Tasan, Murat; Charloteaux, Benoît ULg et al

in Cell (2014), 159(5), 1212-26

Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a ... [more ▼]

Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a broader" human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots" of the genomic revolution." [less ▲]

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See detailAn Efficient Algorithm to Perform Multiple Testing in Epistasis Screening
Van Lishout, François ULg; Cattaert, Tom ULg; Mahachie John, Jestinah ULg et al

Conference (2011, December 13)

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown exponentially over the last few years. It has been marked by promising methodological developments ... [more ▼]

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown exponentially over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. In main-effects detection, this is not a problem since the memory required is thus proportional to the number of SNPs. In contrast, gene-gene interaction studies will require a memory proportional to the squared amount of SNPs. A genome wide epistasis would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. Methods: In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MB-MDR-2.6.2 and compared to MB-MDR's first implementation as an R-package (Calle et al., Bioinformatics 2010). We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn's disease. Results: The sequential version of MBMDR-2.6.2 is approximately 5,500 times faster than its R counterparts. The parallel version (tested on a cluster composed of 14 blades, containing each 4 quad-cores Intel Xeon CPU E5520@2.27 GHz) is approximately 900,000 times faster than the latter, for results of the same quality on the simulated data. It analyses all gene-gene interactions of a dataset of 100,000 SNPs typed on 1000 individuals within 4 days. Our program found 14 SNP-SNP interactions with a p-value less than 0.05 on the real-life Crohn’s disease data. Conclusions: Our software is able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory. A new implementation to reach genome wide epistasis screening is under construction. In the context of Crohn's disease, MBMDR-2.6.2 found signal in regions well known in the field and our results could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype associations. [less ▲]

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See detailProtein-protein interactions and networks: forward and reverse edgetics.
Charloteaux, Benoît ULg; Zhong, Quan; Dreze, Matija et al

in Castrillo, J. I.; Oliver, S. G. (Eds.) Yeast Systems Biology, Methods in Molecular Biology 759 (2011)

Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In ... [more ▼]

Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In interactome networks that are modeled as nodes (macromolecules) connected by edges (interactions), these alterations can be thought of as node removal and edge-specific or "edgetic" perturbations, respectively. Here we present two complementary strategies, forward and reverse edgetics, to investigate the phenotypic outcomes of edgetic perturbations of binary protein-protein interaction networks. Both approaches are based on the yeast two-hybrid system (Y2H). The first allows the determination of the interaction profile of proteins encoded by alleles with known phenotypes to identify edgetic alleles. The second is used to directly isolate edgetic alleles for subsequent in vivo characterization. [less ▲]

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See detailEvidence for Network Evolution in an Arabidopsis Interactome Map
Arabidopsis Interactome Mapping Consortium; Braun, Pascal; Carvunis, Anne-Ruxandra et al

in Science (2011), 333(6042), 601-607

Plants have unique features that evolved in response to their environments and ecosystems. A full account of the complex cellular networks that underlie plant-specific functions is still missing. We ... [more ▼]

Plants have unique features that evolved in response to their environments and ecosystems. A full account of the complex cellular networks that underlie plant-specific functions is still missing. We describe a proteome-wide binary protein-protein interaction map for the interactome network of the plant Arabidopsis thaliana containing about 6200 highly reliable interactions between about 2700 proteins. A global organization of plant biological processes emerges from community analyses of the resulting network, together with large numbers of novel hypothetical functional links between proteins and pathways. We observe a dynamic rewiring of interactions following gene duplication events, providing evidence for a model of evolution acting upon interactome networks. This and future plant interactome maps should facilitate systems approaches to better understand plant biology and improve crops. [less ▲]

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See detailStructural features conferring dual Geranyl/Farnesyl diphosphate synthase activity to an aphid prenyltransferase
Vandermoten, Sophie ULg; Santini, Sébastien; Haubruge, Eric ULg et al

in Insect Biochemistry and Molecular Biology (2009), 39(10), 707-716

In addition to providing lipid chains for protein prenylation, short-chain isoprenyl diphosphate synthases (scIPPSs) play a pivotal role in the biosynthesis of numerous mevalonate pathway end-products ... [more ▼]

In addition to providing lipid chains for protein prenylation, short-chain isoprenyl diphosphate synthases (scIPPSs) play a pivotal role in the biosynthesis of numerous mevalonate pathway end-products, including insect juvenile hormone and terpenoid pheromones. For this reason, they are being considered as targets for pesticide development. Recently, we characterized an aphid scIPPS displaying dual geranyl diphosphate (GPP; C10)/farnesyl diphosphate (FPP; C15) synthase activity in vitro. To identify the mechanism(s) responsible for this dual activity, we assessed the product selectivity of aphid scIPPSs bearing mutations at Gln107 and/or Leu110, the fourth and first residue upstream from the “first aspartate-rich motif” (FARM), respectively. All but one resulted in significant changes in product chain-length selectivity, effectively increasing the production of either GPP (Q107E, L110W) or FPP (Q107F, Q107F–L110A); the other mutation (L110A) abolished activity. Although some of these effects could be attributed to changes in steric hindrance within the catalytic cavity, molecular dynamics simulations identified other contributing factors, including residue-ligand Van der Waals interactions and the formation of hydrogen bonds or salt bridges between Gln107 and other residues across the catalytic cavity, which constitutes a novel product chain-length determination mechanism for scIPPSs. Thus the aphid enzyme apparently evolved to maintain the capacity to produce both GPP and FPP through a balance between these mechanisms. [less ▲]

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See detailStudy of thermomyces ianuginosa lipase in the presence of tributyrylglycerol and water
Santini, Sébastien; Crowet, Jean-Marc ULg; Thomas, Annick ULg et al

in Biophysical Journal (2009), 96(12), 4814-4825

The Thermomyces lanuginosa lipase has been extensively studied in industrial and biotechnological research because of its potential for triacylglycerol transformation. This protein is known to catalyze ... [more ▼]

The Thermomyces lanuginosa lipase has been extensively studied in industrial and biotechnological research because of its potential for triacylglycerol transformation. This protein is known to catalyze both hydrolysis at high water contents and transesterification in quasi-anhydrous conditions. Here, we investigated the Thermomyces lanuginosa lipase structure in solution in the presence of a tributyrin aggregate using 30 ns molecular-dynamics simulations. The water content of the active-site groove was modified between the runs to focus on the protein-water molecule interactions and their implications for protein structure and protein-lipid interactions. The simulations confirmed the high plasticity of the lid fragment and showed that lipid molecules also bind to a secondary pocket beside the lid. Together, these results strongly suggest that the lid plays a role in the anchoring of the protein to the aggregate. The simulations also revealed the existence of a polar channel that connects the active-site groove to the outside solvent. At the inner extremity of this channel, a tyrosine makes hydrogen bonds with residues interacting with the catalytic triad. This system could function as a pipe (polar channel) controlled by a valve (the tyrosine) that could regulate the water content of the active site. [less ▲]

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See detailThe "Tilted Peptide Theory" links membrane insertion properties and fusogenicity of viral fusion peptides.
Charloteaux, Benoît ULg; Lorin, Aurélien; Brasseur, Robert ULg et al

in Protein & Peptide Letters (2009), 16(7), 718-25

Class I fusion glycoproteins of viruses are involved in the fusion between viral envelope and cell membrane. A region located in the N-terminal domain of these glycoproteins, called the fusion peptide, is ... [more ▼]

Class I fusion glycoproteins of viruses are involved in the fusion between viral envelope and cell membrane. A region located in the N-terminal domain of these glycoproteins, called the fusion peptide, is essential for fusion. Fusion peptides are able to induce by themselves in vitro membrane fusion. In this paper, we review the properties of those peptides related to their fusogenicity, in particular the correlation existing between their ability to insert obliquely in membranes and fusogenicity. This relation notably allows predicting successfully the minimal region of some fusion peptides sufficient to induce significant in vitro fusion. The notion of obliquity and fusogenicity is discussed in terms of the existing proposed mechanisms for viral fusion. [less ▲]

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See detailPepLook: An innovative in silico tool for determination of structure, polymorphism and stability of peptides
Thomas, Annick ULg; Deshayes, Sebastien; Decaffmeyer, Marc et al

in Advances in Experimental Medicine and Biology (2009), 611

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See detail'Edgetic' perturbation of a C. elegans BCL2 ortholog.
Dreze, Matija; Charloteaux, Benoît ULg; Milstein, Stuart et al

in Nature Methods (2009), 6(11), 843-9

Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them ... [more ▼]

Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward. [less ▲]

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See detailEdgetic perturbation models of human inherited disorders.
Zhong, Quan; Simonis, Nicolas; Li, Qian*-Ru et al

in Molecular Systems Biology (2009), 5

Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as 'nodes' and 'edges ... [more ▼]

Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as 'nodes' and 'edges', respectively. Better understanding of genotype-to-phenotype relationships in human disease will require modeling of how disease-causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products ('node removal') and interaction-specific or edge-specific ('edgetic') alterations. Global computational analyses of approximately 50,000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies. [less ▲]

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See detailGenomic location of the bovine growth hormone secretagogue receptor (Ghsr) gene and investigation of genetic polymorphism
Colinet, Frédéric ULg; Vanderick, Sylvie ULg; Charloteaux, Benoît ULg et al

in Animal Biotechnology (2009), 20(1), 28-33

The growth hormone secretagogue receptor (GHSR) is involved in the regulation of energetic homeostasis and GH secretion. In this study, the bovine GHSR gene was mapped to BTA1 between BL26 and BMS4004 ... [more ▼]

The growth hormone secretagogue receptor (GHSR) is involved in the regulation of energetic homeostasis and GH secretion. In this study, the bovine GHSR gene was mapped to BTA1 between BL26 and BMS4004. Two different bovine GHSR CDS (GHSR1a and GHSR1b) were sequenced. Six polymorphisms (five SNPs and one 3-bp indel) were also identified, three of them leading to amino acid variations L24V, D194N, and Del R242. These variations are located in the extracellular N-terminal end, the exoloop 2, and the cytoloop 3 of the receptor, respectively. [less ▲]

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See detailDetermination Of The Minimal Fusion Peptide Of Hiv, Siv And Blv Fusion Glycoproteins
Lorin, A.; Charloteaux, Benoît ULg; Lins, Laurence ULg et al

in Peptides For Youth - the Proceedings of the 20th American Peptidesymposium (2009), 611

The entry of enveloped viruses into target cells requires the fusion between the viral envelope and the target cell membrane. In the case of many viruses like HIV, SIV and BLV, the fusion is mediated by ... [more ▼]

The entry of enveloped viruses into target cells requires the fusion between the viral envelope and the target cell membrane. In the case of many viruses like HIV, SIV and BLV, the fusion is mediated by class 1 fusion glycoproteins located on the viral envelope. These fusion glycoproteins contain a region at their N-terminal extremity called the “fusion peptide”, which interact with the target membrane. Many mutagenesis studies showed that this region is required for mediating membrane fusion [1]. Moreover, synthetic peptides corresponding to the fusion peptide of many glycoproteins induce membrane fusion in vitro. Despite the large number of studies on synthetic fusion peptides, the region necessary and sufficient to induce optimal membrane fusion is not known. To determine this minimal fusion peptide, we used the “tilted peptide” theory. According to this theory, a helical peptide inserting obliquely into membranes induces fusion [2]. Moreover, the more tilted the peptide is, the more important the fusion is. Then, we postulate that the minimal fusion peptide corresponds to the shortest helical fragment able to insert into the membrane with an angle close to 45°. This peptide was predicted using the IMPALA algorithm, which allow to predict peptide-membrane interactions [3]. Fusogenicity of this peptide was then assessed in liposome lipid-mixing and leakage assays and compared to the fusogenicity of smaller and longer peptides to check the validity of the prediction. This methodology was used to determine successfully the minimal fusion peptide of three viruses, HIV, SIV and BLV. [less ▲]

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See detailIsoprenoid metabolism in aphid : A new target for bioinsecticides development
Vandermoten, Sophie ULg; Charloteaux, Benoît ULg; Santini, Sébastien et al

Poster (2008, July)

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See detailVariability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus
Couvreur, Bernard; Beaufays, Jérôme ULg; Charon, Cedric et al

in PLoS ONE (2008), 3(1),

Background. Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune ... [more ▼]

Background. Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings. We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusions/Significance. Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. [less ▲]

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See detailCharacterization of a novel aphid prenyltransferase displaying dual geranyl/farnesyl diphosphate synthase activity
Vandermoten, Sophie ULg; Charloteaux, Benoît ULg; Santini, S. et al

in FEBS Letters (2008), 582(16), 19281934

We report on the cDNA cloning and characterization of a novel short-chain isoprenyl diphosphate synthase from the aphid Myzus persicae. Of the three IPPS cDNAs we cloned, two yielded prenyltransferase ... [more ▼]

We report on the cDNA cloning and characterization of a novel short-chain isoprenyl diphosphate synthase from the aphid Myzus persicae. Of the three IPPS cDNAs we cloned, two yielded prenyltransferase activity following expression in Escherichia coli; these cDNAs encode identical proteins except for the presence, in one of them, of an N-terminal mitochondrial targeting peptide. Although the aphid enzyme was predicted to be a farnesyl diphosphate synthase by BLASTP analysis, rMpIPPS, when isopentenyl diphosphate and dimethylallyl diphosphate are supplied as substrates, typically generated geranyl diphosphate (C10) as its main product, along with significant quantities of farnesyl diphosphate (C15). Analysis of an MpIPPS homology model pointed to substitutions that could confer GPP/FPP synthase activity to the aphid enzyme. [less ▲]

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See detailDistantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling.
Adam, Benoit; Charloteaux, Benoît ULg; Beaufays, Jérôme ULg et al

in BMC structural biology (2008), 8(1-2), 1-18

BACKGROUND: Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the ... [more ▼]

BACKGROUND: Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions. RESULTS: It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein. CONCLUSION: By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins. [less ▲]

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See detailThe Minimal Fusion Peptide Of Simian Immunodeficiency Virus Corresponds To The 11 First Residues Of Gp32
Lorin, A.; Lins, Laurence ULg; Stroobant, V. et al

in Journal of Peptide Science (2008), 14(4), 423-8

We had previously predicted successfully the minimal fusion peptides (FPs) of the human immunodeficiency virus 1 (HIV-1) gp41 and the bovine leukemia virus (BLV) gp30 using an original approach based on ... [more ▼]

We had previously predicted successfully the minimal fusion peptides (FPs) of the human immunodeficiency virus 1 (HIV-1) gp41 and the bovine leukemia virus (BLV) gp30 using an original approach based on the obliquity/fusogenicity relationship of tilted peptides. In this paper, we have used the same method to predict the shortest FP capable of inducing optimal fusion in vitro of the simian immunodeficiency virus (SIV) mac isolate and of other SIVs and human immunodeficiency virus (HIV-2) isolates. In each case, the 11-residue-long peptide was predicted as the minimal FP. For the SIV mac isolate, liposome lipid-mixing and leakage assays confirmed that this peptide is the shortest peptide inducing optimal fusion in vitro, being therefore the minimal FP. These results are another piece of evidence that the tilted properties of FPs are important for the fusion process and that our method can be used to predict the minimal FPs of other viruses. [less ▲]

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See detailIn Silico tilted properties of the 67-78 fragment of alpha-synuclein are responsible for membrane destabilization and neurotoxicity
Crowet, Jean-Marc ULg; Lins, Laurence ULg; Dupiereux-Fettweis, Ingrid ULg et al

in Proteins-Structure Function and Bioinformatics (2007), 68(4), 936-947

Alpha-synuclein is a 140 residue protein associated with Parkinson's disease. Intraneural inclusions called Lewy bodies and Lewy neurites are mainly composed of alpha-synuclein aggregated into amyloid ... [more ▼]

Alpha-synuclein is a 140 residue protein associated with Parkinson's disease. Intraneural inclusions called Lewy bodies and Lewy neurites are mainly composed of alpha-synuclein aggregated into amyloid fibrils. Other amyloidogenic proteins, such as the beta amyloid peptide involved in Alzheimer's disease and the prion protein (PrP) associated with Creuztfeldt-Jakob's disease, are known to possess "tilted peptides". These peptides are short protein fragments that adopt an oblique orientation at a hydrophobic/hydrophilic interface, which enables destabilization of the membranes. In this paper, sequence analysis and molecular modelling predict that the 67-78 fragment of alpha-synuclein is a tilted peptide. Its destabilizing properties were tested experimentally. The alpha-synuclein 67-78 peptide is able to induce lipid mixing and leakage of unilamellar liposomes. The neuronal toxicity, studied using human neuroblastoma cells, demonstrated that the alpha-synuclein 67-78 peptide induces neurotoxicity. A mutant designed by molecular modelling to be amphipathic was shown to be significantly less fusogenic and toxic than the wild type. In conclusion, we have identified a tilted peptide in alpha-synuclein, which could be involved in the toxicity induced during amyloidogenesis of alpha-synuclein. [less ▲]

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See detailDetermination Of The Minimal Fusion Peptide Of Bovine Leukemia Virus Gp30
Lorin, A.; Lins, Laurence ULg; Stroobant, V. et al

in Biochemical and Biophysical Research Communications (2007), 355(3), 649-53

In this study, we determined the minimal N-terminal fusion peptide of the gp30 of the bovine leukemia virus on the basis of the tilted peptide theory. We first used molecular modelling to predict that the ... [more ▼]

In this study, we determined the minimal N-terminal fusion peptide of the gp30 of the bovine leukemia virus on the basis of the tilted peptide theory. We first used molecular modelling to predict that the gp30 minimal fusion peptide corresponds to the 15 first residues. Liposome lipid-mixing and leakage assays confirmed that the 15-residue long peptide induces fusion in vitro and that it is the shortest peptide inducing optimal fusion since longer peptides destabilize liposomes to the same extent but not shorter ones. The 15-residue long peptide can thus be considered as the minimal fusion peptide. The effect of mutations reported in the literature was also investigated. Interestingly, mutations related to glycoproteins unable to induce syncytia in cell-cell fusion assays correspond to peptides predicted as non-tilted. The relationship between obliquity and fusogenicity was also confirmed in vitro for one tilted and one non-tilted mutant peptide. [less ▲]

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