The Experts below are selected from a list of 1500 Experts worldwide ranked by ideXlab platform
Jeremy C Smith - One of the best experts on this subject based on the ideXlab platform.
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structure based group a streptococcal vaccine design Helical Wheel homology predicts antibody cross reactivity among streptococcal m protein derived peptides
Journal of Biological Chemistry, 2020Co-Authors: Michelle P Aranha, Thomas A Penfound, Jay A Spencer, Rupesh Agarwal, Jerome Baudry, James B Dale, Jeremy C SmithAbstract:Group A streptococcus (Strep A) surface M protein, an alpha-Helical coiled-coil dimer, is a vaccine target and a major determinant of streptococcal virulence. The sequence-variable N-terminal region of the M protein defines the M type and also contains epitopes that promote opsonophagocytic killing of streptococci. Recent reports have reported considerable cross-reactivity among different M types, suggesting the prospect of identifying cross-protective epitopes that would constitute a broadly protective multivalent vaccine against Strep A isolates. Here, we have used a combination of immunological assays, structural biology, and cheminformatics to construct a recombinant M protein-based vaccine that included six Strep A M peptides that were predicted to elicit antisera that would cross-react with an additional 15 nonvaccine M types of Strep A. Rabbit antisera against this recombinant vaccine cross-reacted with 10 of the 15 nonvaccine M peptides. Two of the five nonvaccine M peptides that did not cross-react shared high sequence identity (>/=50%) with the vaccine peptides, implying that high sequence identity alone was insufficient for cross-reactivity among the M peptides. Additional structural analyses revealed that the sequence identity at corresponding polar Helical-Wheel heptad sites between vaccine and nonvaccine peptides accurately distinguishes cross-reactive from non-cross-reactive peptides. On the basis of these observations, we developed a scoring algorithm based on the sequence identity at polar heptad sites. When applied to all epidemiologically important M types, this algorithm should enable the selection of a minimal number of M peptide-based vaccine candidates that elicit broadly protective immunity against Strep A.
Hervé Lecoeur - One of the best experts on this subject based on the ideXlab platform.
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A flavivirus protein M-derived peptide directly permeabilizes mitochondrial membranes, triggers cell death and reduces human tumor growth in nude mice.
Apoptosis, 2009Co-Authors: Magali Brabant, Ludwig Baux, Richard Casimir, Jean Paul Briand, Olivier Chaloin, Mathieu Porceddu, Nelly Buron, David Chauvier, Myriam Lassalle, Hervé LecoeurAbstract:Dengue viruses belong to the Flavivirus family and are responsible for hemorrhagic fever in Human. Dengue virus infection triggers apoptosis especially through the expression of the small membrane (M) protein. Using isolated mitochondria, we found that synthetic peptides containing the C-terminus part of the M ectodomain caused apoptosis-related mitochondrial membrane permeabilization (MMP) events. These events include matrix swelling and the dissipation of the mitochondrial transmembrane potential (DeltaPsi(m)). Protein M Flavivirus sequence alignments and Helical Wheel projections reveal a conserved distribution of charged residues. Moreover, when combined to the cell penetrating HIV-1 Tat peptide transduction domain (Tat-PTD), this sequence triggers a caspase-dependent cell death associated with DeltaPsi(m) loss and cytochrome c release. Mutational approaches coupled to functional screening on isolated mitochondria resulted in the selection of a protein M derived sequence containing nine residues with potent MMP-inducing properties on isolated mitochondria. A chimeric peptide composed of a Tat-PTD linked to the 9-mer entity triggers MMP and cell death. Finally, local administration of this chimeric peptide induces growth inhibition of xenograft prostate PC3 tumors in immuno-compromised mice, and significantly enhances animal survival. Together, these findings support the notion of using viral genomes as valuable sources to discover mitochondria-targeted sequences that may lead to the development of new anticancer compounds.
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A flavivirus protein M-derived peptide directly permeabilizes mitochondrial membranes, triggers cell death and reduces human tumor growth in nude mice
Apoptosis, 2009Co-Authors: Magali Brabant, Ludwig Baux, Richard Casimir, Jean Paul Briand, Olivier Chaloin, Mathieu Porceddu, Nelly Buron, David Chauvier, Myriam Lassalle, Hervé LecoeurAbstract:Dengue viruses belong to the Flavivirus family and are responsible for hemorrhagic fever in Human. Dengue virus infection triggers apoptosis especially through the expression of the small membrane (M) protein. Using isolated mitochondria, we found that synthetic peptides containing the C-terminus part of the M ectodomain caused apoptosis-related mitochondrial membrane permeabilization (MMP) events. These events include matrix swelling and the dissipation of the mitochondrial transmembrane potential (ΔΨ_m). Protein M Flavivirus sequence alignments and Helical Wheel projections reveal a conserved distribution of charged residues. Moreover, when combined to the cell penetrating HIV-1 Tat peptide transduction domain (Tat-PTD), this sequence triggers a caspase-dependent cell death associated with ΔΨ_m loss and cytochrome c release. Mutational approaches coupled to functional screening on isolated mitochondria resulted in the selection of a protein M derived sequence containing nine residues with potent MMP-inducing properties on isolated mitochondria. A chimeric peptide composed of a Tat-PTD linked to the 9-mer entity triggers MMP and cell death. Finally, local administration of this chimeric peptide induces growth inhibition of xenograft prostate PC3 tumors in immuno-compromised mice, and significantly enhances animal survival. Together, these findings support the notion of using viral genomes as valuable sources to discover mitochondria-targeted sequences that may lead to the development of new anticancer compounds.
Anthony Watts - One of the best experts on this subject based on the ideXlab platform.
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Assessing the effects of time and spatial averaging in ^15N chemical shift/^15N-^1H dipolar correlation solid state NMR experiments
Journal of Biomolecular NMR, 2003Co-Authors: Suzana K. Straus, Walter R.p. Scott, Anthony WattsAbstract:The effect of time and spatial averaging on ^15N chemical shift/^1H-^15N dipolar correlation spectra, i.e., PISEMA spectra, of α-Helical membrane peptides and proteins is investigated. Three types of motion are considered: (a) Librational motion of the peptide planes in the α-helix; (b) rotation of the helix about its long axis; and (c) wobble of the helix about a nominal tilt angle. A 2ns molecular dynamics simulation of helix D of bacteriorhodopsin is used to determine the effect of librational motion on the spectral parameters. For the time averaging, the rotation and wobble of this same helix are modelled by assuming either Gaussian motion about the respective angles or a uniform distribution of a given width. For the spatial averaging, regions of possible ^15N chemical shift/^1H-^15N dipolar splittings are computed for a distribution of rotations and/or tilt angles of the helix. The computed spectra show that under certain motional modes the ^15N chemical shift/^1H-^15N dipolar pairs for each of the residues do not form patterns which mimic Helical Wheel patterns. As a result, the unambiguous identification of helix tilt and helix rotation without any resonance assignments or on the basis of a single assignment may be difficult.
Stanley J. Opella - One of the best experts on this subject based on the ideXlab platform.
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A solid-state NMR index of Helical membrane protein structure and topology.
Journal of Magnetic Resonance, 2000Co-Authors: Francesca M. Marassi, Stanley J. OpellaAbstract:The secondary structure and topology of membrane proteins can be described by inspection of two-dimensional 1H–15N dipolar coupling/15N chemical shift polarization inversion spin exchange at the magic angle spectra obtained from uniformly 15N-labeled samples in oriented bilayers. The characteristic Wheel-like patterns of resonances observed in these spectra reflect Helical Wheel projections of residues in both transmembrane and in-plane helices and hence provide direct indices of the secondary structure and topology of membrane proteins in phospholipid bilayers. We refer to these patterns as PISA (polarity index slant angle) Wheels. The transmembrane helix of the M2 peptide corresponding to the pore-lining segment of the acetylcholine receptor and the membrane surface helix of the antibiotic peptide magainin are used as examples.
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Structure and interactions of magainin antibiotic peptides in lipid bilayers: a solid-state nuclear magnetic resonance investigation.
Biophysical Journal, 1992Co-Authors: Burkhard Bechinger, Michael Zasloff, Stanley J. OpellaAbstract:Many organisms use antibiotic peptides as a defensemechanism, thereby supplementing or replacing theimmune system (1). Magainins are a family of 21 to 26residue peptides found in the skin and other organs offrogs (2, 3) with a broad spectrum of antibacterial,antifungal, and tumorcidal activity (2-4).They disruptthe electrochemical ionic gradient across cell membranes, probably by forming oligomeric peptide ionchannels (4-6). Whereas these peptides show stronginteractionswith bacterial and acidic model membranes(2, 7, 8), they do not lyse formed circulating vertebrateblood cells (3, 4). Multidimensional solution nuclearmagnetic resonance (NMR) experiments show thatmagainin is unstructured in aqueous solution and exhibits a high a-helixcontent in trifluoroethanollwater (9)and in micelles (Shon, K., M. Zasloff, and S. J. Opella,unpublished data). Helical Wheel analysis indicates thatsuch a helix is amphipathic. Solid-stateNMR spectroscopy was used to study the structure, dynamics andinteractions ofmagainins associated with lipid bilayers.
Robert W Olafson - One of the best experts on this subject based on the ideXlab platform.
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cloning and structure function analysis of the leishmania donovani kinetoplastid membrane protein 11
Biochemical Journal, 1995Co-Authors: Armando Jardim, Sheri Hanson, Buddy Ullman, W D Mccubbin, Robert W OlafsonAbstract:This report describes the complete translated gene sequence, predicted secondary structure and lipid bilayer association of a novel kinetoplastid membrane protein (KMP-11) from Leishmania donovani promastigotes. KMP-11 was previously referred to as the lipophosphoglycan-associated protein (LPGAP). The isolation, species distribution and chemical characterization, including a partial protein sequence analysis and post-translational modifications, of this major membrane component have been described [Jardim, Funk, Caprioli and Olafson (1995) Biochem. J. 305, 307-313]. C.d. measurements of KMP-11 indicated a very high Helical content estimated to be approximately 86% in trifluoroethanol. This was in agreement with computer-based secondary-structure analyses which predicted KMP-11 to be almost exclusively alpha-Helical, with the protein adopting a helix-loop-helix motif. Arrangement of the residues located in the putative Helical regions on an Edmundson Helical Wheel showed that this molecule could have a strongly amphipathic conformation and provided an explanation for how such a highly charged protein might be inserted into the plasma membrane. Evidence in support of KMP-11 association with lipid bilayers was provided by showing that KMP-11 could mediate carboxyfluorescein release from liposomes. These findings suggested that KMP-11 may function in part to increase bilayer pressure, stabilizing molecules such as lipophosphoglycan within the parasite pellicular membrane.
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CLONING AND STRUCTURE-FUNCTION ANALYSIS OF THE LEISHMANIA DONOVANI KINETOPLASTID MEMBRANE PROTEIN-11
Biochemical Journal, 1995Co-Authors: Armando Jardim, Sheri Hanson, Buddy Ullman, W D Mccubbin, Cyril M. Kay, Robert W OlafsonAbstract:This report describes the complete translated gene sequence, predicted secondary structure and lipid bilayer association of a novel kinetoplastid membrane protein (KMP-11) from Leishmania donovani promastigotes. KMP-11 was previously referred to as the lipophosphoglycan-associated protein (LPGAP). The isolation, species distribution and chemical characterization, including a partial protein sequence analysis and post-translational modifications, of this major membrane component have been described [Jardim, Funk, Caprioli and Olafson (1995) Biochem. J. 305, 307-313]. C.d. measurements of KMP-11 indicated a very high Helical content estimated to be approximately 86% in trifluoroethanol. This was in agreement with computer-based secondary-structure analyses which predicted KMP-11 to be almost exclusively alpha-Helical, with the protein adopting a helix-loop-helix motif. Arrangement of the residues located in the putative Helical regions on an Edmundson Helical Wheel showed that this molecule could have a strongly amphipathic conformation and provided an explanation for how such a highly charged protein might be inserted into the plasma membrane. Evidence in support of KMP-11 association with lipid bilayers was provided by showing that KMP-11 could mediate carboxyfluorescein release from liposomes. These findings suggested that KMP-11 may function in part to increase bilayer pressure, stabilizing molecules such as lipophosphoglycan within the parasite pellicular membrane.