INTERACTION BETWEEN THE BETA-AMYLOID PEPTIDE PRECURSOR AND HISTONES

The function of the β-amyloid peptide precursors (β-APPs) remains undefined. In a search for ligands of β-APP we found that the most prominent β-APP-binding proteins were histones. To measure the specificity of binding the secreted or extracellular form of β-APP(751), β-APP-S, was purified from recombinant baculovirus-infected Sf-9 cells and was labeled with iodine-125. The labeled β-APP-S bound to each of the histones, which had previously been adsorbed to nitrocellulose membranes. Differences in their apparent affinities were small. β-APP-S did not bind to histones incorporated into chromatin. β-APP-S bound relatively weakly to fibronectin, laminin, collagen type I, or collagen type IV. It did not bind to other basic proteins tested, myelin basic protein, or cytochrome c. The β-APP-S-histone complex adhered to most filters and gel media, which precluded a direct determination of its stability. The apparent dissociation constant of β-APP-S bound to histone-4-Sepharose was about 30 nM. Although β-APP normally does not contact histones, it may bind those that are released from damaged cells. A function of β-APP may be to bind and recycle substances such as histones, proteases, and matrix proteins from the extracellular medium. © 1993 Academic Press. All rights reserved.