title: Charge-based binding of complement component C1q to the Alzheimer amyloid beta-peptide.
abstract: Activation of the classical pathway in Alzheimer's disease derives from the binding of the first protein, subcomponent C1q, to the amyloid beta-peptide (A beta). Analysis of the binding of C1q to A beta by competitive enzyme-linked immunosorbent assay shows that A beta fragments 1-16 and 1-28 but not 12-28 and 17-42 are capable of inhibiting the A beta/C1q interaction, implicating the A beta 1-11 region as the C1q binding site. Binding is also shown to be inhibited by conditions of high ionic strength, suggesting that charged side chains in the A beta 1-11 region are critical to the A beta/c1q interaction. Ultrastructural evidence of binding is provided by platinum replica electron microscopy. Along with a previous demonstration of the 14-26 region of the C1q A chain as the A beta binding site, these findings suggest that attractions between a negative charge cluster in A beta 1-11 and a positive charge cluster in C1qA14-26 mediate the binding of A beta and C1q.
authors.affiliation: Sun Health Research Institute, Sun City, AZ 85372, USA.
authors.forename: S
authors.initials: S
authors.lastname: Webster
authors.forename: B
authors.initials: B
authors.lastname: Bonnell
authors.forename: J
authors.initials: J
authors.lastname: Rogers
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D015922:Complement C1q / Q000378:metabolism*; D003171:Complement Pathway, Classical; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D015922:Complement C1q