Prediction of peptide structure: How far are we?

Thomas, A. G.; Deshayes, Sébastien; Decaffmeyer, Marc; Eyck, Marie Hélène Van; Charloteaux, Benoît; Brasseur, Robert

doi:10.1002/prot.21151

Cited by 72 publications

(66 citation statements)

References 40 publications

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“…The position of the proline residue is indicated. B, spline image of the 99 three-dimensional models calculated using PepLook (49). All models are fitted by adjusting their backbone atoms (N-C-CϭO) to those of the lowest energy structure (the Prime), the three-dimensional model of lower energy using Qmol.…”

Section: Discussionmentioning

confidence: 99%

“…The 6-nm gold particles were enhanced using an R-Gent SE-EM silver enhancing kit (Aurion). Immunolabeled sections were counterstained with uranyl acetate and lead citrate and then observed using a transmission electron microscope (JEM-1200EX, JEOL, Tokyo, Japan (49) to calculate the populations of threedimensional models of caveolin sequence fragments. The Nand C-ends of every peptide were NH and CO to take into account their central positions in the protein sequence.…”

Section: Construction Of Flag Epitope-tagged Caveolin-1 Expressionmentioning

confidence: 99%

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The Role of Proline in the Membrane Re-entrant Helix of Caveolin-1

Aoki

Thomas

Decaffmeyer

et al. 2010

Journal of Biological Chemistry

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Caveolin-1 has a segment of hydrophobic amino acids comprising approximately residues 103-122. We have performed an in silico analysis of the conformational preference of this segment of caveolin-1 using PepLook. We find that there is one main group of stable conformations corresponding to a hydrophobic U bent model that would not traverse the membrane. Furthermore, the calculations predict that substituting the Pro 110 residue with an Ala will change the conformation to a straight hydrophobic helix that would traverse the membrane. We have expressed the P110A mutant of caveolin-1, with a FLAG tag at the N terminus, in HEK 293 cells. We evaluate the topology of the proteins with confocal immunofluorescence microscopy in these cells. We find that FLAG tag at the N terminus of the wild type caveolin-1 is not reactive with antibodies unless the cell membrane is permeabilized with detergent. This indicates that in these cells, the hydrophobic segment of this protein is not transmembrane but takes up a bent conformation, making the protein monotopic. In contrast, the FLAG tag at the N terminus of the P110A mutant is equally exposed to antibodies, before and after membrane permeabilization. We also find that the P110A mutation causes a large reduction of endocytosis of caveolae, cellular lipid accumulation, and lipid droplet formulation. In addition, we find that this mutation markedly reduces the ability of caveolin-1 to form structures with the characteristic morphology of caveolae or to partition into the detergent-resistant membranes of these cells. Thus, the single Pro residue in the membrane-inserting segment of caveolin-1 plays an important role in both the membrane topology and localization of the protein as well as its functions.Caveolae are specialized domains of the plasma membrane found in most cell types and particularly abundant in highly differentiated cells, such as endothelial cells, adipocytes, or muscle cells. They were described as invaginations of the plasma membrane (1, 2). Caveolae appear to have a number of functions, including roles in signal transduction, lipid exchange, cell entry, and intracellular delivery of bacterial toxins, viruses, and growth factors (3-13), but the molecular aspects of their formation and functions are still being unraveled (14). Electron microscopy allows the visualization of caveolae as 50 -100-nm flask-shaped invaginations of the plasma membrane or as circularized single or clustered vesicles underneath the plasma membrane. Caveolae are specialized membrane microdomains enriched in sphingolipids, cholesterol, and receptor proteins. It is also the site of NO production and of cholesterol efflux from the cell. Several isoforms of caveolin are characteristic proteins of caveolae (15, 16).Caveolin inserts into membranes of phosphatidylcholine in a cholesterol-dependent manner (17) and is anchored to the membrane with a hydrophobic segment comprising residues 105-125 as well as with three palmitoyl chains attached to Cys residues. Palmitoylated proteins are known to tra...

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Section: Discussionmentioning

confidence: 99%

Section: Construction Of Flag Epitope-tagged Caveolin-1 Expressionmentioning

confidence: 99%

The Role of Proline in the Membrane Re-entrant Helix of Caveolin-1

Aoki

Thomas

Decaffmeyer

et al. 2010

Journal of Biological Chemistry

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“…20 This method requires several successive steps of calculation. At each step, a random population of 10,000 conformations of DGKɛ 18-42 is generated and the energy of all conformations is calculated using the force field described below.…”

Section: Peplook Methods (Boltzmann Stochastic Method)mentioning

confidence: 99%

“…As previously described by Thomas et al,20 the stability of residues was scored as the ratio (in percent) of their mean force potential values in the calculated models to their reference mean force potential values in a large series of stably folded proteins. 21 Structures with a mean stability score of 100 are considered as stable as in proteins.…”

Section: Modelingmentioning

confidence: 99%

Determination of the Topology of the Hydrophobic Segment of Mammalian Diacylglycerol Kinase Epsilon in a Cell Membrane and Its Relationship to Predictions from Modeling

Decaffmeyer

Shulga

Dicu

et al. 2008

Journal of Molecular Biology

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“…PB based approaches have been proved to be effective in prediction based on protein sequence-structure relationships Li et al, 2009;Tyagi et al, 2009b). Several other applications based on the PB structural alphabet have also given successful results Dudev and Lim, 2007;Faure et al, 2009;Thomas et al, 2006;Tyagi et al, 2008). The characteristics of our structural alphabet have been compared with those of 8 other structural alphabets.…”

Section: Protein Blocksmentioning

confidence: 99%

Species specific amino acid sequence–protein local structure relationships: An analysis in the light of a structural alphabet

Brevern

Joseph

2011

Journal of Theoretical Biology

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To cite this version:Alexandre De Brevern, Agnel Praveen Joseph. Species specific amino acid sequence-protein local structure relationships: An analysis in the light of a structural alphabet.: species sequence -structure relationship. Journal of Theoretical Biology, Elsevier, 2011, 276 (1) AbstractProtein structure analysis and prediction methods are based on non-redundant data extracted from the available protein structures, regardless of the species from which the protein originates. Hence, these datasets represent the global knowledge on protein folds, which constitutes a generic distribution of amino acid sequence -protein structure (AAS-PS) relationships. In this study, we try to elucidate whether the AAS-PS relationship could possess specificities depending on the specie.For this purpose, we have chosen three different species: Saccharomyces cerevisiae, Plasmodium falciparum and Arabidopsis thaliana. We analyzed the AAS-PS behaviors of the proteins from these three species and compared it to the "expected" distribution of a classical non-redundant databank. With the classical secondary structure description, only slight differences in amino acid preferences could be observed. With a more precise description of local protein structures (Protein Blocks), significant changes could be highlighted.Saccharomyces cerevisiae's AAS-PS relationship is close to the general distribution, while striking differences are observed in the case of Arabidopsis thaliana. Plasmodium falciparum is the most distant one.This study presents some interesting view-points on AAS-PS relationship. Certain species exhibit unique preferences for amino acids to be associated with protein local structural elements. Thus, AAS-PS relationships are species dependant. These results can give useful insights for improving prediction methodologies which take the species specific information into account.

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Prediction of peptide structure: How far are we?

Cited by 72 publications

References 40 publications

The Role of Proline in the Membrane Re-entrant Helix of Caveolin-1

The Role of Proline in the Membrane Re-entrant Helix of Caveolin-1

Determination of the Topology of the Hydrophobic Segment of Mammalian Diacylglycerol Kinase Epsilon in a Cell Membrane and Its Relationship to Predictions from Modeling

Species specific amino acid sequence–protein local structure relationships: An analysis in the light of a structural alphabet

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