Bulletin of the American Physical Society
APS March Meeting 2013
Volume 58, Number 1
Monday–Friday, March 18–22, 2013; Baltimore, Maryland
Session N43: Focus Session: Protein Misfolding and Aggregation III |
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Sponsoring Units: DCP DBIO Chair: Elsa Yan, Yale University Room: Hilton Baltimore Holiday Ballroom 2 |
Wednesday, March 20, 2013 11:15AM - 11:27AM |
N43.00001: Structural Transformation and Aggregation of cc-beta Peptides Into Amyloid Proto-fibrils Yuba Bhandari, Timothy Steckmann, Prem Chapagain, Bernard Gerstman The study of amyloid fibrils has important implications in understanding and treatment of various neurodegenerative diseases such as Alzheimer's and Parkinson's. During the formation of amyloid fibrils, peptide polymers manifest fascinating physical behavior by undergoing complicated structural transformations. We examine the behavior of a small engineered peptide called cc-beta, that was designed to mimic the structural changes of the much larger, naturally occurring amyloid beta proteins. Molecular dynamics (MD) simulations are performed to uncover the underlying physics that is responsible for the large scale structural transformations. By using implicit solvent replica exchange MD simulations, we examined the behavior of 12 peptides, initially arranged in four different cc-beta alpha helix trimers. We observed various intermediate stages of aggregation, as well as an organized proto-fibril beta aggregate. We discuss the time evolution and the various interactions involved in the structural transformation. [Preview Abstract] |
Wednesday, March 20, 2013 11:27AM - 11:39AM |
N43.00002: Gelation, Phase Behavior and Dynamics of Beta-Lactoglobulin Amyloid Fibrils at Varying Concentrations and Ionic Strengths Raffaele Mezzenga, Sreenath Bolisetty, Ludger Harnau, Jin-Mi Jung We discuss the thermodynamic and dynamic behavior of Beta-lactoglobulin fibrils in a vast region of the concentration-ionic strength phase diagram, by combining static, dynamic and depolarized light scattering (SLS, DLS, DDLS), small angle neutron scattering (SANS), and cryo-TEM. We focus on the region of the phase diagram where ionic strength and concentration changes induce transitions in gelation and lyotropic liquid crystalline behavior. Increase in ionic strength, by NaCl salt, causes the phase transitions from nematic to gel phases. Increase in fibril concentration induces first a phase transition from an isotropic to a nematic phase; further increase induces the formation of a gel phase. SANS and osmotic compressibility calculated by SLS measurements, capture the main features of the IN transition of Beta-lactoglobulin protein fibrils. The form and structure factors measured by scattering experiments are analyzed by polymer reference interaction site model (PRISM). Dynamics of the protein fibrils at different concentrations, measured by polarized and depolarized dynamic light scattering, shows both individual and collective diffusion after the IN transition. cryo-TEM images further demonstrate the alignment of the protein fibrils, quantified by a 2D order parameter. [Preview Abstract] |
Wednesday, March 20, 2013 11:39AM - 11:51AM |
N43.00003: Amyloid fibril networks nucleated under oscillatory shear Kiersten Batzli, Brian Love The process of amyloid fibril formation is of interest due to the link between these self-aggregating proteins and the progression of neurodegenerative disease. More recently, research has been directed at the exploitation of self-assembly properties of amyloid proteins for use as templates for nanowires and fibrillar networks. Insulin is an ideal protein for these purposes due to the ease of aggregation, as well as the large aspect ratio and high chemical stability of the produced fibrils. Insulin in pH 2 solution quickly forms aggregates in the presence of 65 $^{\circ}$C heat. We have investigated the effect of oscillatory shear on the nucleation and growth of amyloid fibrillar networks using rheology and TEM to characterize the mechanical properties and structure of the network respectively. We contrast networks nucleated under oscillatory shear with networks nucleated in static and agitated conditions, and discuss network properties in the context of use in templating nanostructures. We find that the structural characteristics of the formed networks, including the density of fibrils, are affected by shear during the nucleation phase of amyloid growth. [Preview Abstract] |
Wednesday, March 20, 2013 11:51AM - 12:27PM |
N43.00004: Amyloid Structure In Vitro and In Vivo Invited Speaker: Robert Tycko Solid state nuclear magnetic resonance (NMR) measurements can provide unique information about the structural properties of proteins in noncrystalline states that are of interest from both the biophysical and the biomedical perspectives. I will discuss recent results from my lab's efforts to characterize the molecular structures of amyloid fibrils, especially the A$\beta $ peptide fibrils that are associated with Alzheimer's disease. From a combination of solid state NMR and electron microscopy measurements, we have developed full structural models for 40-residue wild-type A$\beta $ fibrils that form in vitro and contain parallel $\beta $-sheets with 2-fold and 3-fold overall rotational symmetry. We have recently discovered that the ``Iowa mutant'' (D23N-A$\beta )$ peptide can also form metastable fibrils with a surprising antiparallel $\beta $-sheet structure. And we are in the process of investigating A$\beta $ fibril structures that develop in human brain tissue. In addition to recent results, I will briefly describe recent advances in methodology that contribute to this work. [Preview Abstract] |
Wednesday, March 20, 2013 12:27PM - 1:03PM |
N43.00005: Yeast prion architecture explains how proteins can be genes Invited Speaker: Reed Wickner Prions (infectious proteins) transmit information without an accompanying DNA or RNA. Most yeast prions are self-propagating amyloids that inactivate a normally functional protein. A single protein can become any of several prion variants, with different manifestations due to different amyloid structures. We showed that the yeast prion amyloids of Ure2p, Sup35p and Rnq1p are folded in-register parallel beta sheets using solid state NMR dipolar recoupling experiments, mass-per-filament-length measurements, and filament diameter measurements. The extent of beta sheet structure, measured by chemical shifts in solid-state NMR and acquired protease-resistance on amyloid formation, combined with the measured filament diameters, imply that the beta sheets must be folded along the long axis of the filament. We speculate that prion variants of a single protein sequence differ in the location of these folds. Favorable interactions between identical side chains must hold these structures in-register. The same interactions must guide an unstructured monomer joining the end of a filament to assume the same conformation as molecules already in the filament, with the turns at the same locations. In this way, a protein can template its own conformation, in analogy to the ability of a DNA molecule to template its sequence by specific base-pairing. [Preview Abstract] |
Wednesday, March 20, 2013 1:03PM - 1:39PM |
N43.00006: Molecular mechanisms for neurodegeneration Invited Speaker: Hilal Lashuel |
Wednesday, March 20, 2013 1:39PM - 1:51PM |
N43.00007: ABSTRACT HAS BEEN MOVED TO J45.00003 |
Wednesday, March 20, 2013 1:51PM - 2:03PM |
N43.00008: Self-Assembly of Peptides at the Air/Water Interface Mehmet Sayar Peptides are commonly used as building blocks for design and development of novel materials with a variety of application areas ranging from drug design to biotechnology. The precise control of molecular architecture and specific nature of the nonbonded interactions among peptides enable aggregates with well defined structural and functional properties. The interaction of peptides with interfaces leads to dramatic changes in their conformational and aggregation behavior. In this talk, I will discuss our research on the interplay of intermolecular forces and influence of interfaces. In the first part the amphiphilic nature of short peptide oligomers and their behavior at the air/water interface will be discussed. The surface driving force and its decomposition will be analyzed. In the second part aggregation of peptides in bulk water and at an interface will be discussed. Different design features which can be tuned to control aggregation behavior will be analyzed. \\[4pt] [1] O. Engin \& M.S. ``Adsorption, Folding and Packing of an Amphiphilic Peptide at the Air/Water Interface,'' J. Phys. Chem. B 116 (7), 2198-2207 (2012)\\[0pt] [2] O. Engin, A. Villa, M.S. \& H. Berk, ``Driving Forces for Adsorption of Amphiphilic Peptides to Air-Water Interface,'' J. Phys. Chem. B 114, 11093-11101 (2010) [Preview Abstract] |
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