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- Structure of Core Domain of Fibril-Forming PHF/Tau Fragments...Structure of Core Domain of Fibril-Forming PHF/Tau Fragments
Biophysical Journal, Volume 90, Issue 5, 1 March 2006, Pages 1774-1789
Hideyo Inouye, Deepak Sharma, Warren J. Goux and Daniel A. Kirschner
AbstractShort peptide sequences within the microtubule binding domain of the protein Tau are proposed to be core nucleation sites for formation of amyloid fibrils displaying the paired helical filament (PHF) morphology characteristic of neurofibrillary tangles. To study the structure of these proposed nucleation sites, we analyzed the x-ray diffraction patterns from the assemblies formed by a variety of PHF/tau-related peptide constructs containing the motifs VQIINK (PHF6*) in the second repeat and VQIVYK (PHF6) in the third repeat of tau. Peptides included: tripeptide acetyl-VYK-amide (AcVYK), tetrapeptide acetyl-IVYK-amide (AcPHF4), hexapeptide acetyl-VQIVYK-amide (AcPHF6), and acetyl-GKLDLSNVQKDNIKHGSPVDLSKVT-amide (AcTR4). All diffraction patterns showed reflections at spacings of 4.7Å, 3.8Å, and ∼8–10Å, which are characteristic of an orthogonal unit cell of -sheets having dimensions =9.4Å, =6.6Å, and =∼8–10Å (where , , and are the lattice constants in the H-bonding, chain, and intersheet directions). The sharp 4.7Å reflections indicate that the -crystallites are likely to be elongated along the H-bonding direction and in a cross- conformation. The assembly of the AcTR4 peptide, which contains both the PHF6 and PHF6* motifs, consisted of twisted sheets, as indicated by a unique fanning of the diffuse equatorial scattering and meridional accentuation of the (210) reflection at 3.8Å spacing. The diffraction data for AcVYK, AcPHF4, and AcPHF6 all were consistent with ∼50Å-wide tubular assemblies having double-walls, where -strands constitute the walls. In this structure, the peptides are H-bonded together in the fiber direction, and the intersheet direction is radial. The positive-charged lysine residues face the aqueous medium, and tyrosine-tyrosine aromatic interactions stabilize the intersheet (double-wall) layers. This particular contact, which may be involved in PHF fibril formation, is proposed here as a possible aromatic target for anti-tauopathy drugs.
Abstract | Full Text | PDF (793 kb) - An fMRI study of the selective activation of human extrastri...An fMRI study of the selective activation of human extrastriate form vision areas by radial and concentric gratings
Current Biology, Volume 10, Issue 22, 14 November 2000, Pages 1455-1458
Frances Wilkinson, Thomas W James, Hugh R Wilson, Joseph S Gati, Ravi S Menon and Melvyn A Goodale
SummaryThe ventral form vision pathway of the primate brain comprises a sequence of areas that include V1, V2, V4 and the inferior temporal cortex (IT) . Although contour extraction in the V1 area and responses to complex images, such as faces, in the IT have been studied extensively, much less is known about shape extraction at intermediate cortical levels such as V4. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that the human V4 is more strongly activated by concentric and radial patterns than by conventional sinusoidal gratings. This is consistent with global pooling of local V1 orientations to extract concentric and radial shape information in V4. Furthermore, concentric patterns were found to be effective in activating the fusiform face area. These findings support recent psychophysical and physiological data indicating that analysis of concentric and radial structure represents an important aspect of processing at intermediate levels of form vision.
Summary | Full Text | PDF (233 kb) - Impact of Chemical and Structural Anisotropy on the Electrop...Impact of Chemical and Structural Anisotropy on the Electrophoretic Mobility of Spherical Soft Multilayer Particles: The Case of Bacteriophage MS2
Biophysical Journal, Volume 94, Issue 8, 15 April 2008, Pages 3293-3312
Jérémie Langlet, Fabien Gaboriaud, Christophe Gantzer and Jérôme F.L. Duval
AbstractWe report a theoretical investigation of the electrohydrodynamic properties of spherical soft particles composed of permeable concentric layers that differ in thickness, soft material density, chemical composition, and flow penetration degree. Starting from a recent numerical scheme developed for the computation of the direct-current electrophoretic mobility () of diffuse soft bioparticles, the dependence of on the electrolyte concentration and solution pH is evaluated taking the known three-layered structure of bacteriophage MS2 as a supporting model system (bulk RNA, RNA-protein bound layer, and coat protein). The electrokinetic results are discussed for various layer thicknesses, hydrodynamic flow penetration degrees, and chemical compositions, and are discussed on the basis of the equilibrium electrostatic potential and hydrodynamic flow field profiles that develop within and around the structured particle. This study allows for identifying the cases where the electrophoretic mobility is a function of the inner structural and chemical specificity of the particle and not only of its outer surface properties. Along these lines, we demonstrate the general inapplicability of the notions of zeta potential () and surface charge for quantitatively interpreting electrokinetic data collected for such systems. We further shed some light on the physical meaning of the isoelectric point. In particular, numerical and analytical simulations performed on structured soft layers in indifferent electrolytic solution demonstrate that the isoelectric point is a complex ionic strength-dependent signature of the flow permeation properties and of the chemical and structural details of the particle. Finally, the electrophoretic mobilities of the MS2 virus measured at various ionic strength levels and pH values are interpreted on the basis of the theoretical formalism aforementioned. It is shown that the electrokinetic features of MS2 are to a large extent determined not only by the external proteic capsid but also by the chemical composition and hydrodynamic flow permeation of/within the inner RNA-protein bound layer and bulk RNA part of the bacteriophage. The impact of virus aggregation, as revealed by decreasing diffusion coefficients for decreasing pH values, is also discussed.
Abstract | Full Text | PDF (743 kb) - …more
Copyright © 1995 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 68, Issue 5, 1661-1670, 1 May 1995
doi:10.1016/S0006-3495(95)80391-7
Research Article
Radial packing, order, and disorder in collagen fibrils
D.J. Hulmes, T.J. Wess, D.J. Prockop and P. Fratzl
Department of Biochemistry, University of Edinburgh, United Kingdom.
Abstract
Collagen fibrils resemble smectic, liquid crystals in being highly ordered axially but relatively disordered laterally. In some connective tissues, x-ray diffraction reveals three-dimensional crystallinity in the molecular packing within fibrils, although the continued presence of diffuse scatter indicates significant underlying disorder. In addition, several observations from electron microscopy suggest that the molecular packing is organized concentrically about the fibril core. In the present work, theoretical equatorial x-ray diffraction patterns for a number of models for collagen molecular packing are calculated and compared with the experimental data from tendon fibrils. None of the models suggested previously can account for both the crystalline Bragg peaks and the underlying diffuse scatter. In addition, models in which any of the nearest-neighbor, intermolecular vectors are perpendicular to the radial direction are inconsistent with the observed radial orientation of the principal approximately 4 nm Bragg spacing. Both multiple-start spiral and concentric ring models are devised in which one of the nearest-neighbor vectors is along the radial direction. These models are consistent with the radial orientation of the approximately 4 nm spacing, and energy minimization results in radially oriented crystalline domains separated by disordered grain boundaries. Theoretical x-ray diffraction patterns show a combination of sharp Bragg peaks and underlying diffuse scatter. Close agreement with the observed equatorial diffraction pattern is obtained. The concentric ring model is consistent with the observation that the diameters of collagen fibrils are restricted to discrete values.
