title: Charge substitution shows that repulsive electrostatic interactions impede the oligomerization of Alzheimer amyloid peptides.
abstract: The strong pH dependence of A beta oligomerization could arise from favorable intermolecular charge-charge interactions between His and carboxylate groups, or, alternatively, by mutual electrostatic repulsion of peptide molecules. To test between these two possibilities, the pH dependence of the oligomerization of A beta and three charge substitution variants with Asp, Glu and His substituted by Ala is measured. All four peptides oligomerize, as detected by thioflavin T fluorescence, turbidity, and amyloid fibril formation; therefore, specific charge-charge interactions are nonessential for oligomerization. The strong negative correlation between net charge and oligomerization indicates that electrostatic repulsion between A beta monomers impedes their association.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ont., Canada M5G 2M9.
authors.forename: Meng
authors.initials: M
authors.lastname: Guo
authors.forename: Paul M
authors.initials: PM
authors.lastname: Gorman
authors.forename: Manuel
authors.initials: M
authors.lastname: Rico
authors.forename: Avijit
authors.initials: A
authors.lastname: Chakrabartty
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Laurents
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000682:Amyloid / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D055672:Static Electricity
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)