title: 125I-labeled ApoE binds competitively to beta(1-40) fibrils with pathological chaperone proteins.
abstract: Radiolabeled Apolipoprotein E (Apo E) was used in a competitive binding filtration assay to amyloid fibrils preformed from beta(1-40) peptide as a probe of the binding sites for proteins either found in senile plaques in Alzheimer's Disease brain or reported to be associated with the soluble peptide. Apo E, Apo J, Apo A-I, Apo B, laminin, complement components C3 and C4, and alpha 1-antichymotrypsin all displayed sub-micromolar apparent affinities for the Apo E binding site on fibrils. Transthyretin, alpha 2-macroglobulin, amyloid P protein, heparan sulfate proteoglycan, complement component C1q, chondroitin sulfate A, and GM1 ganglioside were much less effective. The epsilon 2, epsilon 3, and epsilon 4 isoforms of Apo E showed different affinities for fibrils and lipidation of these lipoproteins made little difference. Other fibrillar beta-peptides also bound Apo E, with A beta 40-A beta 42 > A beta(12-28); A beta(25-35) = 0. A series of soluble beta-peptides and fragments failed to effect Apo E binding. Thus, both conformational and quaternary structural features are important in high affinity binding of Apo E to A beta 40 fibrils. Different amyloid plaque-associated molecules apparently associate with alternative primary and secondary structural features on fibrils.
authors.affiliation: Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105-1047, USA. Harry.LeVine@wl.com
authors.forename: H
authors.initials: H
authors.lastname: LeVine
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D006801:Humans; D007457:Iodine Radioisotopes; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D007457:Iodine Radioisotopes; D010446:Peptide Fragments