References of "Decaffmeyer, Marc"
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See detailPeptides As Drugs: Myth Or Reality?
Decaffmeyer, Marc ULg; Thomas, Annick ULg; Brasseur, Robert ULg

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2008), 12(1),

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See detailRelationships between the orientation and the structural properties of peptides and their membrane interactions.
Lins, Laurence ULg; Decaffmeyer, Marc ULg; Thomas, Annick ULg et al

in Biochimica et biophysica acta (2008), 1778(7-8), 1537-44

Physical properties of membranes, such as fluidity, charge or curvature influence their function. Proteins and peptides can modulate those properties and conversely, the lipids can affect the activity and ... [more ▼]

Physical properties of membranes, such as fluidity, charge or curvature influence their function. Proteins and peptides can modulate those properties and conversely, the lipids can affect the activity and/or the structure of the former. Tilted peptides are short hydrophobic protein fragments characterized by an asymmetric distribution of their hydrophobic residues when helical. They were detected in viral fusion proteins and in proteins involved in different biological processes that need membrane destabilization. Those peptides and non lamellar lipids such as PE or PA appear to cooperate in the lipid destabilization process by enhancing the formation of negatively-curved domains. Such highly bent lipidic structures could favour the formation of the viral fusion pore intermediates or that of toroidal pores. Structural flexibility appears as another crucial property for the interaction of peptides with membranes. Computational analysis on another kind of lipid-interacting peptides, i.e. cell penetrating peptides (CPP) suggests that peptides being conformationally polymorphic should be more prone to traverse the bilayer. Future investigations on the structural intrinsic properties of tilted peptides and the influence of CPP on the bilayer organization using the techniques described in this chapter should help to further understand the molecular determinants of the peptide/lipid inter-relationships. [less ▲]

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See detailDetermination Of The Topology Of The Hydrophobic Segment Of Mammalian Diacylglycerol Kinase Epsilon In A Cell Membrane And Its Relationship To Predictions From Modeling
Decaffmeyer, Marc ULg; Shulga, Yv.; Dicu, Ao. et al

in Journal of Molecular Biology (2008), 383(4), 797-809

The epsilon isoform of diacylglycerol kinase (DGKepsilon) is unique among mammalian DGKs in having a segment of hydrophobic amino acids comprising approximately residues 20 to 41. Several algorithms ... [more ▼]

The epsilon isoform of diacylglycerol kinase (DGKepsilon) is unique among mammalian DGKs in having a segment of hydrophobic amino acids comprising approximately residues 20 to 41. Several algorithms predict this segment to be a transmembrane (TM) helix. Using PepLook, we have performed an in silico analysis of the conformational preference of the segment in a hydrophobic environment comprising residues 18 to 42 of DGKepsilon. We find that there are two distinct groups of stable conformations, one corresponding to a straight helix that would traverse the membrane and the second corresponding to a bent helix that would enter and leave the same side of the membrane. Furthermore, the calculations predict that substituting the Pro32 residue in the hydrophobic segment with an Ala will cause the hydrophobic segment to favor a TM orientation. We have expressed the P32A mutant of DGKepsilon, with a FLAG tag (an N-terminal 3xFLAG epitope tag) at the amino terminus, in COS-7 cells. We find that this mutation causes a large reduction in both k(cat) and K(m) while maintaining k(cat)/K(m) constant. Specificity of the P32A mutant for substrates with polyunsaturated acyl chains is retained. The P32A mutant also has higher affinity for membranes since it is more difficult to extract from the membrane with high salt concentration or high pH compared with the wild-type DGKepsilon. We also evaluated the topology of the proteins with confocal immunofluorescence microscopy using NIH 3T3 cells. We find that the FLAG tag at the amino terminus of the wild-type enzyme is not reactive with antibodies unless the cell membrane is permeabilized with detergent. We also demonstrate that at least a fraction of the wild-type DGKepsilon is present in the plasma membrane and that comparable amounts of the wild-type and P32A mutant proteins are in the plasma membrane fraction. This indicates that in these cells the hydrophobic segment of the wild-type DGKepsilon is not TM but takes up a bent conformation. In contrast, the FLAG tag at the amino terminus of the P32A mutant is exposed to antibody both before and after membrane permeabilization. This modeling approach thus provides an explanation, not provided by simple predictive algorithms, for the observed topology of this protein in cell membranes. The work also demonstrates that the wild-type DGKepsilon is a monotopic protein. [less ▲]

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See detailStructural Polymorphism Of Two Cpp: An Important Parameter Of Activity
Deshayes, S.; Decaffmeyer, Marc ULg; Brasseur, Robert ULg et al

in Biochimica et Biophysica Acta-Biomembranes (2008), 1778(5), 1197-205

Despite numerous investigations, the important structural features of Cell Penetrating Peptides (CPPs) remain unclear as demonstrated by the difficulties encountered in designing new molecules. In this ... [more ▼]

Despite numerous investigations, the important structural features of Cell Penetrating Peptides (CPPs) remain unclear as demonstrated by the difficulties encountered in designing new molecules. In this study, we focused our interest on Penetratin and Transportan and several of their variants. Penetratin W48F and Penetratin W48F/W56F exhibit a reduced and a complete lack of cellular uptake, respectively; TP07 and TP10 present a similar cellular uptake as Transportan and TP08, TP13 and TP15 display no or weak internalization capacity. We applied the algorithmic method named PepLook to analyze the peptide polymorphism. The study reveals common conformational characteristics for the CPPs and their permeable variants: they all are polymorphic. Negative, non permeable, mutants share the opposite feature since they are monomorphic. Finally, we support the hypothesis that structural polymorphism may be crucial since it provides peptides with the possibility of adapting their conformation to medium hydrophobicity and or to partner diversity. [less ▲]

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See detailPrediction Of Peptide Structure: How Far Are We?
Thomas, Annick ULg; Deshayes, S.; Decaffmeyer, Marc ULg et al

in Proteins-Structure Function and Bioinformatics (2006), 65(4), 889-97

Rational design of peptides is a challenge, which would benefit from a better knowledge of the rules of sequence-structure-function relationships. Peptide structures can be approached by spectroscopy and ... [more ▼]

Rational design of peptides is a challenge, which would benefit from a better knowledge of the rules of sequence-structure-function relationships. Peptide structures can be approached by spectroscopy and NMR techniques but data from these approaches too frequently diverge. Structures can also be calculated in silico from primary sequence information using three algorithms: Pepstr, Robetta, and PepLook. The most recent algorithm, PepLook introduces indexes for evaluating structural polymorphism and stability. For peptides with converging experimental data, calculated structures from PepLook and, to a lesser extent from Pepstr, are close to NMR models. The PepLook index for polymorphism is low and the index for stability points out possible binding sites. For peptides with divergent experimental data, calculated and NMR structures can be similar or, can be different. These differences are apparently due to polymorphism and to different conditions of structure assays and calculations. The PepLook index for polymorphism maps the fragments encoding disorder. This should provide new means for the rational design of peptides. [less ▲]

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See detailTp0453, A Concealed Outer Membrane Protein Of Treponema Pallidum, Enhances Membrane Permeability
Hazlett, Kro.; Cox, Dl.; Decaffmeyer, Marc ULg et al

in Journal of Bacteriology (2005), 187(18), 6499-508

he outer membrane of Treponema pallidum, the non-cultivable agent of venereal syphilis, contains a paucity of protein(s) which has yet to be definitively identified. In contrast, the outer membranes of ... [more ▼]

he outer membrane of Treponema pallidum, the non-cultivable agent of venereal syphilis, contains a paucity of protein(s) which has yet to be definitively identified. In contrast, the outer membranes of gram-negative bacteria contain abundant immunogenic membrane-spanning beta-barrel proteins mainly involved in nutrient transport. The absence of orthologs of gram-negative porins and outer membrane nutrient-specific transporters in the T. pallidum genome predicts that nutrient transport across the outer membrane must differ fundamentally in T. pallidum and gram-negative bacteria. Here we describe a T. pallidum outer membrane protein (TP0453) that, in contrast to all integral outer membrane proteins of known structure, lacks extensive beta-sheet structure and does not traverse the outer membrane to become surface exposed. TP0453 is a lipoprotein with an amphiphilic polypeptide containing multiple membrane-inserting, amphipathic alpha-helices. Insertion of the recombinant, non-lipidated protein into artificial membranes results in bilayer destabilization and enhanced permeability. Our findings lead us to hypothesize that TP0453 is a novel type of bacterial outer membrane protein which may render the T. pallidum outer membrane permeable to nutrients while remaining inaccessible to antibody. [less ▲]

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