Alzheimer's beta-amyloid: insights into fibril formation and structure from Congo red binding.
We consider here the chemistry of Congo red (CR), its binding equilibrium to Alzheimer's beta-amyloid, and the kinetics of beta-amyloid formation. Spectroscopic UV/V is measurements for the pH- and time-dependence binding of CR to Abeta analogues are analysed by Scatchard binding and the theory of nucleation-dependent fibril formation. CR likely binds electrostatically to the imidazolium sidechains of histidine residues that are exposed at the surface of amyloid fibrils. As revealed by atomic models of the Abeta protofilament, such as the nanotube beta-helix and parallel beta-sheet, the regular arrangement of histidines likely acts as a template for the end-to-end J-aggregation of CR molecules, which produces a red shift in UV/V is absorption.
Inouye
Hideyo
H
Department of Biology, Boston College, Chestnut Hill, MA 02467-3811, USA.
Kirschner
Daniel A
DA
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D004396:Coloring Agents; D003224:Congo Red; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding
D000682:Amyloid; D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003224:Congo Red