Characterization of the Zn<sup>II</sup> Binding to the Peptide Amyloid‐β<sup>1–16</sup> linked to Alzheimer's Disease

Mekmouche, Yasmina; Coppel, Yannick; Hochgräfe, Katja; Guilloreau, Luc; Talmard, Christine; Mazarguil, Honoré; Faller, Peter

doi:10.1002/cbic.200500057

Cited by 89 publications

(105 citation statements)

References 41 publications

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“…Finally, other results obtained by structural studies, have shown that this peptide has two metal binding sites with higher and lower affinity: copper in high affinity site is coordinated in a planar configuration with three histidines and terminus or Tyr10 and this binding site is able to bind also a zinc ion [21,22,25]. The four aminoacids proposed for zinc binding site are Tyr10, Glu11, Arg5 or the N-terminus [6,[26][27][28][29]. It has been made hypothesis about the presence for both metals in the second low affinity binding site but it is still studying [30][31][32].…”

Section: Introductionmentioning

confidence: 71%

Thermal aggregation of β-lactoglobulin in presence of metal ions

Navarra

Leone

Militello

2007

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 AbstractIn this work, we report a study on the effects of zinc and copper ions on the heat-induced aggregation of β−Lactoglobulin (BLG). Kinetics investigations on aggregates growth by light scattering measurements and on secondary structure changes by FT-IR absorption measurementsshow the different role played by two metals during the whole process. In particular, the presence of zinc in solution promotes the formation of aggregates of BLG at a lower temperature than the copper. Then, fixed the temperature, formation of a large amount of aggregates, with a large dimension, is observed for the Zn-BLG in shorter time; on the contrary, the presence of the copper in solution does not affect the aggregation process but the secondary structure changes and the formation of different stronger intermolecular H-bonds, which probably lead to build a network of bonds that takes towards gelation. Our studies show as time evolution of aggregation process of BLG is dramatically affected by the presence of metal ions in solution and structural protein modifications are induced by different divalent metal ions.

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Section: Introductionmentioning

confidence: 71%

Thermal aggregation of β-lactoglobulin in presence of metal ions

Navarra

Leone

Militello

2007

Biophysical Chemistry

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“…According to several studies, high concentrations of Al and Zn may be associated to the formation of b-amyloid in the brain, which are implicated in Alzheimer's disease (Bush et al 1994;Zatta et al 2002;Kaizer et al 2005;Mekmouche et al 2005); therefore it should not be excluded the hypothesis of these metals being mobilized from the lung, liver or kidney to the brain where they act as neurotoxicants. The levels of apoptotic nuclei, in all organs, were higher in mice from Furnas than in those from Rabo de Peixe.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis, metallothionein, and bioavailable metals in domestic mice (Mus musculus L.) from a human-inhabited volcanic area

et al. 2007

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The influence of extreme environments of volcanic origin over vertebrates and the cellular responses that these may give are almost unknown. The main objectives were to evaluate the exposure of mice to metals in the interior of houses of a small village settled inside a volcanic crater (Furnas, Azores), and the levels of apoptosis and metallothionein in the organs (lung, liver, and kidney) of those animals. Adult mice (Mus musculus) were captured in two areas, one with volcanic activity and the other without it over the last three centuries. In the excised organs, analysis of metals (Al, Cd, Pb, Zn), TUNEL assay for apoptosis, and immunohistochemistry for metallothionein were undertook. Mice from the area with volcanic activity presented higher levels of apoptosis and metallothionein than those from the area without volcanic activity. Such results were in agreement with the differences in metal burdens of the three organs, and interestingly these concentrations were similar to or higher than others found in heavily polluted areas outside the Azores. Thus, there may be a high risk of harmful effects for organisms, including humans, inhabiting areas with volcanism, where hazardous gases and metals in the air are very common during the entire day or even all year round.

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“…Acetylation of the N-terminus does not inhibit zinc binding to the N-terminal fragment Ab(1-16), but the fourth ligand is proposed to be Glu11 in this variant [36]. In the same fragment but without an acetylated N-terminus, Asp1 was suggested to be the fourth ligand [35]. Recently Syme et al published a study on Ab(1-16) and Ab(1-28) in which they also suggested the fourth ligand to be the N-terminus, and indeed an N-terminal-blocked variant of Ab(1-28) showed less effects when zinc was added [45].…”

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confidence: 94%

High‐resolution NMR studies of the zinc‐binding site of the Alzheimer's amyloid β‐peptide

et al. 2006

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Metal binding to the amyloid β‐peptide is suggested to be involved in the pathogenesis of Alzheimer's disease. We used high‐resolution NMR to study zinc binding to amyloid β‐peptide 1–40 at physiologic pH. Metal binding induces a structural change in the peptide, which is in chemical exchange on an intermediate rate, between the apo‐form and the holo‐form, with respect to the NMR timescale. This causes loss of NMR signals in the resonances affected by the binding. Heteronuclear correlation experiments, 15N‐relaxation and amide proton exchange experiments on amyloid β‐peptide 1–40 revealed that zinc binding involves the three histidines (residues 6, 13 and 14) and the N‐terminus, similar to a previously proposed copper‐binding site [Syme CD, Nadal RC, Rigby SE, Viles JH (2004) J Biol Chem279, 18169–18177]. Fluorescence experiments show that zinc shares a common binding site with copper and that the metals have similar affinities for amyloid β‐peptide. The dissociation constant Kd of zinc for the fragment amyloid β‐peptide 1–28 was measured by fluorescence, using competitive binding studies, and that for amyloid β‐peptide 1–40 was measured by NMR. Both methods gave Kd values in the micromolar range at pH 7.2 and 286 K. Zinc also has a second, weaker binding site involving residues between 23 and 28. At high metal ion concentrations, the metal‐induced aggregation should mainly have an electrostatic origin from decreased repulsion between peptides. At low metal ion concentrations, on the other hand, the metal‐induced structure of the peptide counteracts aggregation.

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Characterization of the Zn^II Binding to the Peptide Amyloid‐β^1–16 linked to Alzheimer's Disease

Cited by 89 publications

References 41 publications

Thermal aggregation of β-lactoglobulin in presence of metal ions

Thermal aggregation of β-lactoglobulin in presence of metal ions

Apoptosis, metallothionein, and bioavailable metals in domestic mice (Mus musculus L.) from a human-inhabited volcanic area

High‐resolution NMR studies of the zinc‐binding site of the Alzheimer's amyloid β‐peptide

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Characterization of the ZnII Binding to the Peptide Amyloid‐β1–16 linked to Alzheimer's Disease

Cited by 89 publications

References 41 publications

Thermal aggregation of β-lactoglobulin in presence of metal ions

Thermal aggregation of β-lactoglobulin in presence of metal ions

Apoptosis, metallothionein, and bioavailable metals in domestic mice (Mus musculus L.) from a human-inhabited volcanic area

High‐resolution NMR studies of the zinc‐binding site of the Alzheimer's amyloid β‐peptide

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Characterization of the Zn^II Binding to the Peptide Amyloid‐β^1–16 linked to Alzheimer's Disease