title: Interaction between the beta-amyloid peptide precursor and histones.
abstract: The function of the beta-amyloid peptide precursors (beta-APPs) remains undefined. In a search for ligands of beta-APP we found that the most prominent beta-APP-binding proteins were histones. To measure the specificity of binding the secreted or extracellular form of beta-APP(751), beta-APP-S, was purified from recombinant baculovirus-infected Sf-9 cells and was labeled with iodine-125. The labeled beta-APP-S bound to each of the histones, which had previously been adsorbed to nitrocellulose membranes. Differences in their apparent affinities were small. beta-APP-S did not bind to histones incorporated into chromatin. beta-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 beta-APP-S-histone complex adhered to most filters and gel media, which precluded a direct determination of its stability. The apparent dissociation constant of beta-APP-S bound to histone-4-Sepharose was about 30 nM. Although beta-APP normally does not contact histones, it may bind those that are released from damaged cells. A function of beta-APP may be to bind and recycle substances such as histones, proteases, and matrix proteins from the extracellular medium.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Department of Molecular Biology, Staten Island 10314.
authors.forename: A
authors.initials: A
authors.lastname: Potempska
authors.forename: N
authors.initials: N
authors.lastname: Ramakrishna
authors.forename: H M
authors.initials: HM
authors.lastname: Wisniewski
authors.forename: D L
authors.initials: DL
authors.lastname: Miller
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D003574:Cytochrome c Group; D006657:Histones; D004676:Myelin Basic Protein; D011994:Recombinant Proteins