Tags

Type your tag names separated by a space and hit enter

pH-Dependent Cu(II) coordination to amyloid-β peptide: impact of sequence alterations, including the H6R and D7N familial mutations.
Inorg Chem. 2011 Nov 07; 50(21):11192-201.IC

Abstract

Copper ions have been proposed to intervene in deleterious processes linked to the development of Alzheimer's disease (AD). As a direct consequence, delineating how Cu(II) can be bound to amyloid-β (Aβ) peptide, the amyloidogenic peptide encountered in AD, is of paramount importance. Two different forms of [Cu(II)(Aβ)] complexes are present near physiological pH, usually noted components I and II, the nature of which is still widely debated in the literature, especially for II. In the present report, the phenomenological pH-dependent study of Cu(II) coordination to Aβ and to ten mutants by EPR, CD, and NMR techniques is described. Although only indirect insights can be obtained from the study of Cu(II) binding to mutated peptides, they reveal very useful for better defining Cu(II) coordination sites in the native Aβ peptide. Four components were identified between pH 6 and 12, namely, components I, II, III and IV, in which the predominant Cu(II) equatorial sites are {-NH(2), CO (Asp1-Ala2), N(im) (His6), N(im) (His13 or His14)}, {-NH(2), N(-) (Asp1-Ala2), CO (Ala2-Glu3), N(im)}, {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(im)} and {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(-) (Glu3-Phe4)}, respectively, in line with classical pH-induced deprotonation of the peptide backbone encountered in Cu(II) peptidic complexes formation. The structure proposed for component II is discussed with respect to another coordination model reported in the literature, that is, {CO (Ala2-Glu3), 3 N(im)}. Cu(II) binding to the H6R-Aβ and D7N-Aβ peptides, where the familial H6R and D7N mutations have been linked to early onset of AD, has also been investigated. In case of the H6R mutation, some different structural features (compared to those encountered in the native [Cu(II)(Aβ)] species) have been evidenced and are anticipated to be important for the aggregating properties of the H6R-Aβ peptide in presence of Cu(II).

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Alies B
CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse, France.
Eury H
No affiliation info available
Bijani C
No affiliation info available
Rechignat L
No affiliation info available
Faller P
No affiliation info available
Hureau C
No affiliation info available

MeSH

Alzheimer DiseaseAmino Acid SequenceAmino AcidsAmyloid beta-PeptidesBinding SitesCopperElectron Spin Resonance SpectroscopyHumansHydrogen-Ion ConcentrationMolecular ConformationMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularPoint MutationProtein BindingSolutions

Pub Type(s)

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

Language

eng

PubMed ID

21980910

Citation

Alies, Bruno, et al. "PH-Dependent Cu(II) Coordination to Amyloid-β Peptide: Impact of Sequence Alterations, Including the H6R and D7N Familial Mutations." Inorganic Chemistry, vol. 50, no. 21, 2011, pp. 11192-201.
Alies B, Eury H, Bijani C, et al. PH-Dependent Cu(II) coordination to amyloid-β peptide: impact of sequence alterations, including the H6R and D7N familial mutations. Inorg Chem. 2011;50(21):11192-201.
Alies, B., Eury, H., Bijani, C., Rechignat, L., Faller, P., & Hureau, C. (2011). PH-Dependent Cu(II) coordination to amyloid-β peptide: impact of sequence alterations, including the H6R and D7N familial mutations. Inorganic Chemistry, 50(21), 11192-201. https://doi.org/10.1021/ic201739n
Alies B, et al. PH-Dependent Cu(II) Coordination to Amyloid-β Peptide: Impact of Sequence Alterations, Including the H6R and D7N Familial Mutations. Inorg Chem. 2011 Nov 7;50(21):11192-201. PubMed PMID: 21980910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - pH-Dependent Cu(II) coordination to amyloid-β peptide: impact of sequence alterations, including the H6R and D7N familial mutations. AU - Alies,Bruno, AU - Eury,Hélène, AU - Bijani,Christian, AU - Rechignat,Lionel, AU - Faller,Peter, AU - Hureau,Christelle, Y1 - 2011/10/06/ PY - 2011/10/11/entrez PY - 2011/10/11/pubmed PY - 2012/2/15/medline SP - 11192 EP - 201 JF - Inorganic chemistry JO - Inorg Chem VL - 50 IS - 21 N2 - Copper ions have been proposed to intervene in deleterious processes linked to the development of Alzheimer's disease (AD). As a direct consequence, delineating how Cu(II) can be bound to amyloid-β (Aβ) peptide, the amyloidogenic peptide encountered in AD, is of paramount importance. Two different forms of [Cu(II)(Aβ)] complexes are present near physiological pH, usually noted components I and II, the nature of which is still widely debated in the literature, especially for II. In the present report, the phenomenological pH-dependent study of Cu(II) coordination to Aβ and to ten mutants by EPR, CD, and NMR techniques is described. Although only indirect insights can be obtained from the study of Cu(II) binding to mutated peptides, they reveal very useful for better defining Cu(II) coordination sites in the native Aβ peptide. Four components were identified between pH 6 and 12, namely, components I, II, III and IV, in which the predominant Cu(II) equatorial sites are {-NH(2), CO (Asp1-Ala2), N(im) (His6), N(im) (His13 or His14)}, {-NH(2), N(-) (Asp1-Ala2), CO (Ala2-Glu3), N(im)}, {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(im)} and {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(-) (Glu3-Phe4)}, respectively, in line with classical pH-induced deprotonation of the peptide backbone encountered in Cu(II) peptidic complexes formation. The structure proposed for component II is discussed with respect to another coordination model reported in the literature, that is, {CO (Ala2-Glu3), 3 N(im)}. Cu(II) binding to the H6R-Aβ and D7N-Aβ peptides, where the familial H6R and D7N mutations have been linked to early onset of AD, has also been investigated. In case of the H6R mutation, some different structural features (compared to those encountered in the native [Cu(II)(Aβ)] species) have been evidenced and are anticipated to be important for the aggregating properties of the H6R-Aβ peptide in presence of Cu(II). SN - 1520-510X UR - https://www.unboundmedicine.com/medline/citation/21980910/pH_Dependent_Cu_II__coordination_to_amyloid_β_peptide:_impact_of_sequence_alterations_including_the_H6R_and_D7N_familial_mutations_ L2 - https://doi.org/10.1021/ic201739n DB - PRIME DP - Unbound Medicine ER -