SECONDARY STRUCTURE OF ALZHEIMER'S Ab1-40 BY RAMAN SPECTROSCOPY: EFFECT OF PROTEOLIPOSOME
A.R. Koudinov, N.V. Koudinova, T.T. Berezov, V.Yu.Uvarov and Yu.D. Ivanov
Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation
Amyloid b (Ab) is a major constituent of amyloid deposits in brain tissue of Alzheimer's and Down's syndrome patients and is a normal soluble protein (sAb) of human body. We showed previously that sAb in both normal human plasma and CSF is associated with the HDL. The aim of the present work was to elucidate whether phospholipid as an important HDL structural constituent contributes to sAb to HDL binding and solubility. To this end the effect of dimiristoylphospha-tidylcholine proteoliposomes on the Ab1-40 secondary structure was calculated from the Raman spectra, obtained in the amide-I band, and confirmed by electron microscopy, thioflavine T assay and gel filtration analysis. Conformation of the Ab, calculated for a-helix, b-strand, b-turn and coil was found to be 2:58:26:14 and 13:53:21:13 for lipid free and proteoliposome bound peptide, respectively. These data imply that HDL lipid, and in particular, phospholipid, binding to sAb contributes to the b-peptide solubility in biological fluids and inhibits its fibrillogenic b-strand conformation. Change of this interaction in the disease may drive peptide's polymerization into the brain tissue amyloid fibrils.
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