title: Amyloid-β peptide binds to cytochrome C oxidase subunit 1.
abstract: Extracellular and intraneuronal accumulation of amyloid-beta aggregates has been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of macromolecules has deleterious effects on cellular functions. Mitochondria were found to be the target for amyloid-beta, and mitochondrial dysfunction is well documented in AD. In the present study we have shown for the first time that Aβ 1-42 bound to a peptide comprising the amino-terminal region of cytochrome c oxidase subunit 1. Phage clone, selected after screening of a human brain cDNA library expressed on M13 phage and bearing a 61 amino acid fragment of cytochrome c oxidase subunit 1, bound to Aβ 1-42 in ELISA as well as to Aβ aggregates present in AD brain. Aβ 1-42 and cytochrome c oxidase subunit 1 co-immunoprecipitated from mitochondrial fraction of differentiated human neuroblastoma cells. Likewise, molecular dynamics simulation of the cytochrome c oxidase subunit 1 and the Aβ 1-42 peptide complex resulted in a reliable helix-helix interaction, supporting the experimental results. The interaction between Aβ 1-42 and cytochrome c oxidase subunit 1 may explain, in part, the diminished enzymatic activity of respiratory chain complex IV and subsequent neuronal metabolic dysfunction observed in AD.
authors.affiliation: Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico DF, Mexico.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Hernandez-Zimbron
authors.forename: Jose
authors.initials: J
authors.lastname: Luna-Muñoz
authors.forename: Raul
authors.initials: R
authors.lastname: Mena
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vazquez-Ramirez
authors.forename: Carlos
authors.initials: C
authors.lastname: Kubli-Garfias
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.forename: Karen
authors.initials: K
authors.lastname: Manoutcharian
authors.forename: Goar
authors.initials: G
authors.lastname: Gevorkian
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003576:Electron Transport Complex IV