Amyloidosis of Alzheimer's Aβ peptides: solid‐state nuclear magnetic resonance, electron paramagnetic resonance, transmission electron microscopy, scanning transmission electron microscopy and atomic force microscopy studies

Antzutkin, Oleg N.

doi:10.1002/mrc.1341

Cited by 77 publications

(66 citation statements)

References 128 publications

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“…The identity of the fourth ligand includes tyrosine at position 10 (Tyr10) (16,(19)(20)(21), the N-terminal nitrogen (22), or an undefined carboxylate side chain (23). Our EPR studies indicate that increasing the Cu 2+ above ∼0.3 mol/mol peptide-induced line broadening in the Cu 2+ EPR spectra suggests the presence of dipolar or exchange effects (17,19).…”

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confidence: 82%

Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

et al. 2007

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The Amyloid peptide (A ) of Alzheimer's diseases (AD) is closely linked to the progressive cognitive decline associated with the disease. Cu 2+ ions can induce the de noVo aggregation of the A peptide into non-amyloidogenic aggregates and the production of a toxic species. The mechanism by which Cu 2+ mediates the change from amyloid material toward Cu 2+ induced aggregates is poorly defined. Here we demonstrate that the aggregation state of A 1-42 at neutral pH is governed by the Cu 2+ :peptide molar ratio. By probing amyloid content and total aggregation, we observed a distinct Cu 2+ switching effect centered at equimolar Cu 2+ :peptide ratios. At sub-equimolar Cu 2+ :peptide molar ratios, A 1-42 forms thioflavin-T reactive amyloid; conversely, at supra-equimolar Cu 2+ :peptide molar ratios, A 1-42 forms both small spherical oligomers approximately 10-20 nm in size and large amorphous aggregates. We demonstrate that these insoluble aggregates form spontaneously via a soluble species without the presence of an observable lag phase. In seeding experiments, the Cu 2+ induced aggregates were unable to influence fibril formation or convert into fibrillar material. Aged Cu 2+ induced aggregates are toxic when compared to A 1-42 aged in the absence of Cu 2+ . Importantly, the formation of dityrosine crosslinked A , by the oxidative modification of the peptide, only occurs at equimolar molar ratios and above. The formation of dityrosine adducts occurs following the initiation of aggregation and hence does not drive the formation of the Cu 2+ induced aggregates. These results define the role Cu 2+ plays in modulating the aggregation state and toxicity of A 1-42.

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confidence: 82%

Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

et al. 2007

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“…Several spectroscopic studies have indicated that the copper-binding site of Aβ consists of the three histidine residues His6, His13 and His14 and an as yet undefined fourth ligand; proposed ligands include Tyr10 [19,[38][39][40], the Nterminal nitrogen [30] or an as yet unidentified carboxylate side chain [31,32].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Interaction of β-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study

Drochioiu

Manea

Drăguşanu

et al. 2009

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 AbstractThe stoichiometries and the affinity toward simple and paired metal ions of synthetic amyloid-β(1-40)peptide (Aβ1-40) were investigated by electrospray ion trap mass spectrometry (ESI-MS), circular dichroism (CD), and atomic force microscopy (AFM). The results lead to the working hypothesis that pHdependent metal binding to Aβ1-40 may induce conformational changes, which affect the affinity toward other metals. A significant copper and zinc binding to Aβ1-40 peptide at pH 5.5 was found, whereas nickel ions commonly bind to each molecule of β-amyloid peptide. Some complexes of Aβ1-40 with more than one nickel ion were identified by ESI-MS. In addition, nickel ions proved to enhance Aβ oligomerization. On increasing pH, up to 12 ions of zinc may bind to a single Aβ molecule. Under the same pH and concentration conditions, the binding pattern of the independent copper and silver ions to Aβ1-40 was different from that of the equimolecular mixture of the two metal ions. One might assume that some conformational changes due to water loss altered the capacity of Aβ peptide to bind certain heavy metal ions. As a consequence, copper-silver interaction with the binding process to Aβ1-40 became highly complex. A competition between silver and nickel ions for Aβ1-40 binding sites at high pH was also observed. New strategies were proposed to identify the characteristic signals for some important metal ion-peptide complexes in the spectra recorded at high pH or high concentrations of metal ions. To explain the formation of such a large number of high metal ion-Aβ complexes, we took into consideration the participation of both histidine residues and free amino groups as well as carboxylate ones in the binding process. Finally, CD and AFM studies supported the mass spectrometric data.

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“…30 In addition, membrane proteins, which are characterized by the presence of several extended hydrophobic regions, show very low levels of expression in E. coli. 31 Furthermore, natively unfolded proteins tend to have more charged and fewer hydrophobic amino acids 32 in order to increase their solubility in the absence of the protection against aggregation provided by a folded structure, 19 but despite these features their expression levels are in some cases lower than those of globular proteins, 33 thus indicating the key role played by the native structure in maintaining the solubility of polypeptide chains. 19 …”

Section: Aggregation and Chemical Properties Of Proteinsmentioning

confidence: 99%

Towards quantitative predictions in cell biology using chemical properties of proteins

Vendruscolo

Tartaglia

2008

Mol. BioSyst.

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It has recently been suggested that the concentrations of proteins in the cell are tuned towards their critical values, and that the alteration of this balance often results in misfolding diseases. This concept is intriguing because the in vivo concentrations of proteins are closely regulated by complex cellular processes, while their critical concentrations are primarily determined by the chemical characters of their amino acid sequences. We discuss here how the presence of a link between the upper levels of in vivo concentrations and critical concentrations offers an opportunity to make quantitative predictions in cell biology based on the chemical properties of proteins.

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Amyloidosis of Alzheimer's Aβ peptides: solid‐state nuclear magnetic resonance, electron paramagnetic resonance, transmission electron microscopy, scanning transmission electron microscopy and atomic force microscopy studies

Cited by 77 publications

References 128 publications

Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

Interaction of β-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study

Towards quantitative predictions in cell biology using chemical properties of proteins

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Amyloidosis of Alzheimer's Aβ peptides: solid‐state nuclear magnetic resonance, electron paramagnetic resonance, transmission electron microscopy, scanning transmission electron microscopy and atomic force microscopy studies

Cited by 77 publications

References 128 publications

Concentration Dependent Cu2+Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

Concentration Dependent Cu2+Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

Interaction of β-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study

Towards quantitative predictions in cell biology using chemical properties of proteins

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Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide

Concentration Dependent Cu²⁺Induced Aggregation and Dityrosine Formation of the Alzheimer's Disease Amyloid-β Peptide