A model for structure-dependent binding of Congo red to Alzheimer beta-amyloid fibrils.
The cytotoxic A beta fibril is a logical candidate for the entity causing the initiating damage to neurons in Alzheimer's disease and Down's syndrome. We have derived a model of binding for the dye molecule, Congo red (CR), to a beta-sheet structure of beta-amyloid (1-42). This model is based on the crystal coordinates of CR binding to porcine insulin fibrils from Turnell and Finch. Intact insulin is composed of protein dimers and X-ray diffraction studies show that CR intercalates between two insulin monomers at an interface formed by a pair of antiparallel beta-strands. The intercalation of CR has disrupted the four main-chain hydrogen bonds between the two beta-strands, but they are still tethered with each other through new hydrogen bonds with the CR nitrogen atoms. The CR molecule has been aligned along the homologous stretch of amino acids in Alzheimer beta peptide (two molecules in antiparallel distorted or pseudo beta-sheet conformation) using the crystal coordinates from the Turnell-Finch paper to arrive at a putative structure for CR binding to Alzheimer's amyloid fibrils.
Carter
D B
DB
Central Nervous System Research, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49001, USA.
Chou
K C
KC
D000465:Algorithms; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D004396:Coloring Agents / Q000737:chemistry; D003224:Congo Red / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009412:Nerve Fibers / Q000737:chemistry* / Q000378:metabolism*; D013552:Swine
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D007328:Insulin; D003224:Congo Red