A MODEL FOR STRUCTURE-DEPENDENT BINDING OF CONGO RED TO ALZHEIMER BETA-AMYLOID FIBRILS

The cytotoxic alpha beta fibril is a logical candidate for the entity causing the initiating damage to neurons in Alzheimer's disease and Do wn'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). Th is 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 anti parallel beta-strands. The intercalation of CR has disrupted the four main-chain hydrogen bonds between the two beta-strands, but they are s till tethered with each other through new hydrogen bonds with the CR n itrogen atoms. The CR molecule has been aligned along the homologous s tretch of amino acids in Alzheimer beta peptide (two molecules in anti parallel distorted or pseudo beta-sheet conformation) using the crysta l coordinates from the Turnell-Finch paper to ari ive at a putative st ructure for CR binding to Alzheimer's amyloid fibrils. (C) 1998 Elsevi er Science Inc.