Tracking Internal and Global Diffusive Dynamics During Protein Aggregation by High-Resolution Neutron Spectroscopy
| Autor: | Kevin Pounot, Tilo Seydel, Hussein Chaaban, Giorgio Schirò, Martin Weik, Vito Foderà |
|---|---|
| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut Max von Laue, Department of Pharmacy, University of Copenhagen = Københavns Universitet (KU), IT University of Copenhagen, University of Copenhagen = Københavns Universitet (UCPH), IT University of Copenhagen (ITU), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Protein Conformation Kinetics Beta sheet 02 engineering and technology Protein aggregation Diffusion 03 medical and health sciences Protein Aggregates General Materials Science Physical and Theoretical Chemistry Spectroscopy 030304 developmental biology Neutrons 0303 health sciences [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Chemistry Spectrum Analysis 021001 nanoscience & nanotechnology Neutron spectroscopy Isoelectric point Neutron backscattering Biophysics Muramidase 0210 nano-technology Superstructure (condensed matter) |
| Zdroj: | Journal of Physical Chemistry Letters Journal of Physical Chemistry Letters, American Chemical Society, 2020, 11 (15), pp.6299-6304. ⟨10.1021/acs.jpclett.0c01530⟩ Journal of Physical Chemistry Letters, 2020, 11 (15), pp.6299-6304. ⟨10.1021/acs.jpclett.0c01530⟩ |
| ISSN: | 1948-7185 |
| DOI: | 10.1021/acs.jpclett.0c01530⟩ |
| Popis: | International audience; Proteins can misfold and form either amorphous or organized aggregates with different morphologies and features. Aggregates of amyloid nature are pathological hallmarks in so-called protein conformational diseases, including Alzheimer's and Parkinson's. Evidence prevails that the transient early phases of the reaction determine the aggregate morphology and toxicity. As a consequence, real-time monitoring of protein aggregation is of utmost importance. Here, we employed time-resolved neutron backscattering spectroscopy to follow center-of-mass self-diffusion and nano- to picosecond internal dynamics of lysozyme during aggregation into a specific β-sheet rich superstructure, called particulates, formed at the isoelectric point of the protein. Particulate formation is found to be a one-step process, and protein internal dynamics, to remain unchanged during the entire aggregation process. The time-resolved neutron backscattering spectroscopy approach developed here, in combination with standard kinetics assays, provides a unifying framework in which dynamics and conformational transitions can be related to the different aggregation pathways. |
| Databáze: | OpenAIRE |
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