The beta A4 amyloid precursor protein binding to copper.
Previously it has been shown that the extracellular domain of transmembrane beta A4 amyloid precursor protein (APP) includes binding sites for zinc(II) and for molecules of the extracellular matrix such as collagen, laminin and the heparin sulfate chains of proteoglycans (HSPGs). Here we report that APP also binds copper ions. A copper type II binding site was located within residues 135-155 of the cysteine-rich domain of APP695 which is present in all eight APP splice isoforms known so far. The two essential histidines in the type II copper binding site of APP are conserved in the related protein APLP2. Copper(II) binding is shown to inhibit homophilic APP binding. The identification of a copper(II) binding site in APP suggests that APP and APLP2 may be involved in electron transfer and radical reactions.
Hesse
L
L
Center for Molecular Biology Heidelberg, University Heidelberg, Germany.
Beher
D
D
Masters
C L
CL
Multhaup
G
G
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002614:Chelating Agents; D003300:Copper / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012685:Sepharose; D017386:Sequence Homology, Amino Acid
D016564:Amyloid beta-Protein Precursor; D002614:Chelating Agents; D011993:Recombinant Fusion Proteins; D003300:Copper; D012685:Sepharose