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α-Synuclein (αS) is a protein with multiple conformations and interactions. Natively unfolded in solution, αS accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of αS to remodel vesicles. At molar ratios of 1:5 to 1:40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles ~50 Å in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150-500 Å in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70-100 Å across, are formed. EPR data show that, on cylindrical micelles, αS adopts an extended amphipathic α-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between αS and the micelle suggests that the wedging of its long α-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation.
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http://dx.doi.org/10.1074/jbc.M112.365817 | DOI Listing |
Soft Matter
December 2024
Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
The self-assembly behaviors of rod-coil asymmetric diblock molecular brushes (ADMBs) bearing responsive side chains in a selective solvent are investigated dissipative particle dynamics simulations. By systematically varying the polymerization degree, copolymer concentration, and side chain length, several morphological phase diagrams were constructed. ADMB assemblies exhibited a rich variety of morphologies, including cylindrical micelles, spherical micelles, nanowires, polyhedral micelles, ellipsoid micelles, and large compound micelles.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211, USA.
A significant problem with current influenza vaccines is their reliance on predictions of the most prevalent strains for the upcoming season, with inaccurate forecasts greatly reducing the overall efficacy of the immunization campaign. A universal influenza vaccine, which leverages epitopes conserved across many, if not all, strains of influenza, could reduce the need for extremely accurate forecasting. The highly conserved ectodomain of the influenza M2 protein contains a B cell epitope in the M2 region, making it a promising candidate as a universal influenza vaccine.
View Article and Find Full Text PDFJ Chem Phys
November 2024
São Paulo State University (UNESP), Institute of Biosciences, Humanities and Exact Sciences, 15054-000 São José do Rio Preto, Brazil.
The critical adsorption conditions of polyelectrolytes (PEs) onto planar, cylindrical, and spherical surfaces were obtained by solving the Edwards equation using the Wentzel-Kramers-Brillouin (WKB) method. It demonstrated to provide a suitable analytical approach for all three geometries, in conformity with some experimental results for weakly charged micelles. However, our Monte Carlo simulations implementing approximate solutions of the nonlinear Poisson-Boltzmann equation for highly charged surfaces indicated recently the emergence of a limiting value of ionic strength due to a nonlinear dependence of the electrostatic (ES) potential on the surface-charge density σ.
View Article and Find Full Text PDFBiomacromolecules
December 2024
The Czech Academy of Sciences, Institute of Chemical Process Fundamentals, 165 02 Prague, Czech Republic.
Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.
View Article and Find Full Text PDFSmall
December 2024
Department of Chemistry and National Center of Competence in Research Bio-inspired Materials, University of Fribourg, Chemin du Musée 9, Fribourg, 1700, Switzerland.
The antimicrobial peptide LL-37 is a promising alternative to conventional antibiotics to combat bacteria in suspension and biofilms. Its self-assembly with polar lipids is suggested to improve its potential for therapeutic applications with higher stability against degradation and bioavailability. This study investigates the self-assembly of LL-37 with glyceryl monooleate (GMO), establishing the link between colloidal structure and antimicrobial activity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!