%0 Journal Article
%T Amyloid-汕 Peptide Binds to Cytochrome C Oxidase Subunit 1
%A Luis Fernando Hernandez-Zimbron
%A Jose Luna-Muˋoz
%A Raul Mena
%A Ricardo Vazquez-Ramirez
%A Carlos Kubli-Garfias
%A David H. Cribbs
%A Karen Manoutcharian
%A Goar Gevorkian
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0042344
%X 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 A汕 1每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 A汕 1每42 in ELISA as well as to A汕 aggregates present in AD brain. A汕 1每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 A汕 1每42 peptide complex resulted in a reliable helix-helix interaction, supporting the experimental results. The interaction between A汕 1每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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042344