A beta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies

Autor: Nur Alia Oktaviani, Aleksey Lomakin, Frans A. A. Mulder, Dainan Zhang, Tiernan T. O'Malley, Brian O'Nuallain, George B. Benedek, Michael J. Rowan, Dominic M. Walsh, Sara Linse
Přispěvatelé: Molecular Dynamics
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Protein Conformation
Dimer
PROTEIN FIBRILLOGENESIS
Peptide
Biochemistry
chemistry.chemical_compound
Protein structure
AMYLOID FIBRILS
OLIGOMERS
Cerebellum
PEPTIDE
Evoked Potentials
MOLECULAR PATHOLOGY
Neurons
chemistry.chemical_classification
education.field_of_study
Nuclear magnetic resonance spectroscopy
Alzheimer's disease
Recombinant Proteins
ALZHEIMERS-DISEASE
Monomer
NMR-SPECTROSCOPY
amyloid beta-protein
Dimerization
Amyloid
Stereochemistry
nuclear magnetic resonance (NMR)
DITYROSINE CROSS-LINKS
Population
Cystine
Nerve Tissue Proteins
Alzheimer Disease
Animals
Humans
Rats
Wistar
education
Nuclear Magnetic Resonance
Biomolecular
Molecular Biology
long-term potentiation
Injections
Intraventricular
Amyloid beta-Peptides
synaptic plasticity
SECONDARY NUCLEATION
Cell Biology
Peptide Fragments
Rats
Kinetics
Amino Acid Substitution
Solubility
chemistry
Synapses
Protein Multimerization
Zdroj: Biochemical Journal, 461(3), 413-426. PORTLAND PRESS LTD
O'Malley, T T, Oktaviani, N A, Zhang, D, Lomakin, A, O'Nuallain, B, Linse, S, Benedek, G B, Rowan, M J, Mulder, F A A & Walsh, D M 2014, ' Aβ dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies ', Biochemical Journal, vol. 461, no. 3, pp. 413-426 . https://doi.org/10.1042/BJ20140219
ISSN: 0264-6021
DOI: 10.1042/BJ20140219
Popis: Dimers of A beta (amyloid beta-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [A beta](DiY) (dityrosine cross-linked A beta). For comparison, we used the A beta monomer and a design dimer cross-linked by replacement of Ser(26) with cystine [A beta S26C](2). We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [A beta](DiY) and [A beta S26C](2) have distinct aggregation pathways, they both populate bioactive soluble assemblies for longer durations than A beta monomers. Our results indicate that the link between A beta dimers and Alzheimer's disease results from the ability of dimers to further assemble and form synaptotoxic assemblies that persist for long periods of time.
Databáze: OpenAIRE
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