Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer's disease and other human tauopathies

Autor: Eleonora Minelli, Fulvio Florenzano, Valentina Latina, Gabriele Ciasca, Giuseppe Maulucci, Matteo Nardini, Valentina Palmieri, Giordano Perini, Pietro Calissano, Giuseppina Amadoro, Veronica Corsetti, Marco De Spirito, Massimiliano Papi
Rok vydání: 2019
Předmět:
Alzheimer's disease (AD)
Atomic Force Microscopy (AFM)
Molecular Dynamics (MD) simulation
Small Angle X-ray Scattering (SAXS)
Tau protein
Protein Conformation
Context (language use)
Peptide
tau Proteins
02 engineering and technology
Molecular Dynamics Simulation
Microscopy
Atomic Force
Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI
AMBIENTALI
BIOLOGIA E MEDICINA)
Biochemistry
Pathogenesis
03 medical and health sciences
Structure-Activity Relationship
X-Ray Diffraction
Structural Biology
In vivo
Alzheimer Disease
medicine
Animals
Humans
Amino Acid Sequence
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
Neurons
Microscopy
0303 health sciences
biology
Chemistry
Mechanism (biology)
Neurotoxicity
Atomic Force
General Medicine
021001 nanoscience & nanotechnology
medicine.disease
Amino acid
Rats
Tauopathies
biology.protein
Peptides
0210 nano-technology
Neuroscience
Zdroj: International journal of biological macromolecules 141 (2019): 278–289. doi:10.1016/j.ijbiomac.2019.08.220
info:cnr-pdr/source/autori:Perini G.; Ciasca G.; Minelli E.; Papi M.; Palmieri V.; Maulucci G.; Nardini M.; Latina V.; Corsetti V.; Florenzano F.; Calissano P.; De Spirito M.; Amadoro G./titolo:Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer's disease and other human tauopathies/doi:10.1016%2Fj.ijbiomac.2019.08.220/rivista:International journal of biological macromolecules/anno:2019/pagina_da:278/pagina_a:289/intervallo_pagine:278–289/volume:141
ISSN: 1879-0003
Popis: The intrinsically disordered tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and other human tauopathies. Abnormal post-translational modifications of tau, such as truncation, are causally involved in the onset/development of these neurodegenerative diseases. In this context, the AD-relevant N-terminal fragment mapping between 26 and 44 amino acids of protein (tau26-44) is interesting, being endowed with potent neurotoxic effects in vitro and in vivo. However, the understanding of the mechanism(s) of tau26-44 toxicity is a challenging task because, similarly to the full-length tau, it does not have a unique 3D structure but exists as dynamic ensemble of conformations. Here we use Atomic Force Spectroscopy, Small Angle X-ray Scattering and Molecular Dynamics simulation to gather structural and functional information on the tau26-44. We highlight the presence, the type and the location of its temporary secondary structures and we unveil the occurrence of relevant transient tertiary conformations that could contribute to tau26-44 toxicity. Data are compared with those obtained on the biologically-inactive, reverse-sequence (tau44-26 peptide) which has the same mass, charge, aminoacidic composition as well as the same overall unfolded character of tau26-44.
Databáze: OpenAIRE
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