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New insights into the coordination of Cu(II) by the amyloid-B 16 peptide from Fourier transform IR spectroscopy and isotopic labeling.
J Phys Chem B. 2011 Dec 15; 115(49):14812-21.JP

Abstract

Alzheimer's disease is a neurodegenerative disorder in which the formation of amyloid-β (Aβ) aggregates plays a causative role. There is ample evidence that Cu(II) can bind to Aβ and modulate its aggregation. Moreover, Cu(II) bound to Aβ might be involved in the production of reactive oxygen species, a process supposed to be involved in the Alzheimer's disease. The native Aβ40 contains a high affinity binding site for Cu(II), which is comprised in the N-terminal portion. Thus, Aβ16 (amino acid 1-16 of Aβ) has often been used as a model for Cu(II)-binding to monomeric Aβ. The Cu(II)-binding to Aβ is pH dependent and at pH 7.4, two different type of Cu(II) coordinations exist in equilibrium. These two forms are predominant at pH 6.5 and pH 9.0. In either form, a variety of studies show that the N-terminal Asp and the three His play a key role in the coordination, although the exact binding of these amino acids has not been addressed. Therefore, we studied the coordination modes of Cu(II) at pH 6.5 and 9.0 with the help of Fourier transform infrared (FTIR) spectroscopy. Combined with isotopic labeling of the amino acids involved in the coordination sphere, the data points toward the coordination of Cu(II) via the carboxylate of Asp1 at both pH values in a pseudobridging monovalent fashion. At low pH, His6 binds copper via Nτ, while His13 and His14 are bound via Nπ. At high pH, direct evidence is given on the coordination of Cu(II) via the Nτ atom of His6. Additionally, this study clearly shows the effect of Cu(II) binding on the protonation state of the His residues where a proton displacement takes places on the nitrogen atoms of the imidazole ring.

Authors+Show Affiliations

Institut de Chimie, UMR 7177 Laboratoire de spectroscopie vibrationnelle et électrochimie des biomolécules, Université de Strasbourg 1, Strasbourg, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22026330

Citation

El Khoury, Youssef, et al. "New Insights Into the Coordination of Cu(II) By the amyloid-B 16 Peptide From Fourier Transform IR Spectroscopy and Isotopic Labeling." The Journal of Physical Chemistry. B, vol. 115, no. 49, 2011, pp. 14812-21.
El Khoury Y, Dorlet P, Faller P, et al. New insights into the coordination of Cu(II) by the amyloid-B 16 peptide from Fourier transform IR spectroscopy and isotopic labeling. J Phys Chem B. 2011;115(49):14812-21.
El Khoury, Y., Dorlet, P., Faller, P., & Hellwig, P. (2011). New insights into the coordination of Cu(II) by the amyloid-B 16 peptide from Fourier transform IR spectroscopy and isotopic labeling. The Journal of Physical Chemistry. B, 115(49), 14812-21. https://doi.org/10.1021/jp207328y
El Khoury Y, et al. New Insights Into the Coordination of Cu(II) By the amyloid-B 16 Peptide From Fourier Transform IR Spectroscopy and Isotopic Labeling. J Phys Chem B. 2011 Dec 15;115(49):14812-21. PubMed PMID: 22026330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New insights into the coordination of Cu(II) by the amyloid-B 16 peptide from Fourier transform IR spectroscopy and isotopic labeling. AU - El Khoury,Youssef, AU - Dorlet,Pierre, AU - Faller,Peter, AU - Hellwig,Petra, Y1 - 2011/11/15/ PY - 2011/10/27/entrez PY - 2011/10/27/pubmed PY - 2012/4/5/medline SP - 14812 EP - 21 JF - The journal of physical chemistry. B JO - J Phys Chem B VL - 115 IS - 49 N2 - Alzheimer's disease is a neurodegenerative disorder in which the formation of amyloid-β (Aβ) aggregates plays a causative role. There is ample evidence that Cu(II) can bind to Aβ and modulate its aggregation. Moreover, Cu(II) bound to Aβ might be involved in the production of reactive oxygen species, a process supposed to be involved in the Alzheimer's disease. The native Aβ40 contains a high affinity binding site for Cu(II), which is comprised in the N-terminal portion. Thus, Aβ16 (amino acid 1-16 of Aβ) has often been used as a model for Cu(II)-binding to monomeric Aβ. The Cu(II)-binding to Aβ is pH dependent and at pH 7.4, two different type of Cu(II) coordinations exist in equilibrium. These two forms are predominant at pH 6.5 and pH 9.0. In either form, a variety of studies show that the N-terminal Asp and the three His play a key role in the coordination, although the exact binding of these amino acids has not been addressed. Therefore, we studied the coordination modes of Cu(II) at pH 6.5 and 9.0 with the help of Fourier transform infrared (FTIR) spectroscopy. Combined with isotopic labeling of the amino acids involved in the coordination sphere, the data points toward the coordination of Cu(II) via the carboxylate of Asp1 at both pH values in a pseudobridging monovalent fashion. At low pH, His6 binds copper via Nτ, while His13 and His14 are bound via Nπ. At high pH, direct evidence is given on the coordination of Cu(II) via the Nτ atom of His6. Additionally, this study clearly shows the effect of Cu(II) binding on the protonation state of the His residues where a proton displacement takes places on the nitrogen atoms of the imidazole ring. SN - 1520-5207 UR - https://www.unboundmedicine.com/medline/citation/22026330/New_insights_into_the_coordination_of_Cu_II__by_the_amyloid_B_16_peptide_from_Fourier_transform_IR_spectroscopy_and_isotopic_labeling_ DB - PRIME DP - Unbound Medicine ER -