Time dependence of NMR observables reveals salient differences in the accumulation of early aggregated species between human islet amyloid polypeptide and amyloid-β
| Autor: | Olivier Lequin, Ludovic Carlier, Pierre-Alexandre Spath, Anais R. F. Hoffmann, Lucie Khemtémourian, Lucie Caillon, Lilian Shadai Salazar Vazquez |
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| Přispěvatelé: | Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system Magnetic Resonance Spectroscopy Amyloid Protein Conformation Kinetics General Physics and Astronomy Protein aggregation 010402 general chemistry 01 natural sciences Micelle 03 medical and health sciences chemistry.chemical_compound Protein Aggregates Protein structure Humans [CHIM]Chemical Sciences Magnetization transfer Amino Acid Sequence Physical and Theoretical Chemistry Amyloid beta-Peptides Chemistry Nuclear magnetic resonance spectroscopy 0104 chemical sciences Islet Amyloid Polypeptide 030104 developmental biology Biophysics Thioflavin |
| Zdroj: | Physical Chemistry Chemical Physics Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2018, 20 (14), pp.9561-9573. ⟨10.1039/C7CP07516B⟩ |
| ISSN: | 1463-9076 1463-9084 |
| DOI: | 10.1039/C7CP07516B⟩ |
| Popis: | International audience; Type 2 diabetes mellitus and Alzheimer's disease are characterized by the accumulation of fibrillar amyloid deposits consisting mainly of islet amyloid polypeptide (IAPP) and amyloid-b (Ab), respectively. Fibril formation is a multi-step nucleation process that involves the transient build-up of oligomeric species that are thought to be the most toxic components. To gain more insight into the molecular mechanism of early IAPP aggregated species formation, we performed a combination of direct and indirect biophysical approaches on IAPP and also on Ab42 for the sake of comparison. Thioflavin T fluorescence kinetics measurements revealed a stronger autocatalytic behaviour of IAPP and a weaker concentration dependence of fibrillization half-time t 1/2 , as compared to Ab42. Our NMR experiments highlight the absence of micelle reservoir or supercritical regime in the studied concentration range, indicating that the low concentration dependence of IAPP fibril formation can be ascribed to saturable pathways. IAPP and Ab42 displayed marked differences in formation of oligomeric species, as observed by 1D 1 H, pulsed-field gradient (PFG) diffusion and saturation transfer difference (STD) NMR experiments. A fast equilibrium between monomer and oligomeric species was detected in the case of Ab42 but not IAPP, with a significant build-up of aggregated species, as shown by the time dependence of diffusion coefficient and STD magnetization transfer efficiency during the aggregation process. Altogether our data show significant differences between IAPP and Ab42 regarding the microscopic events of amyloid species formation. |
| Databáze: | OpenAIRE |
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