Multhaup G, Bush A I, Pollwein P, Masters C L
Center for Molecular Biology Heidelberg-ZMBH, University Heidelberg, Germany.
FEBS Lett. 1994 Nov 28;355(2):151-4. doi: 10.1016/0014-5793(94)01176-1.
The Alzheimer's disease beta A4 amyloid precursor protein (APP) has been suggested to be involved in regulation of cell growth, neurite outgrowth and adhesiveness through binding to heparin sulfate proteoglycans. In order to unravel the molecular mechanisms underlying those functions in vitro we show that APP binds in a time dependent and saturable manner to the glycosaminoglycan side-chains of proteoglycans but not to chondroitinsulfate. We also demonstrate an interaction between the high affinity heparin binding site within the carbohydrate domain of APP and the zinc(II) binding site of APP. We show that the affinity for heparin is increased two- to four-fold in the presence of micromolar zinc(II). Thus micromolar concentrations of zinc(II) appear to be able to modulate the binding of APP to heparin side-chains of proteoglycans and as shown previously [Science 265 (1994) 1464-1467] to induce the aggregation of soluble amyloid beta A4 protein.
阿尔茨海默病β A4淀粉样前体蛋白（APP）已被认为通过与硫酸乙酰肝素蛋白聚糖结合参与细胞生长、神经突生长和黏附的调节。为了在体外阐明这些功能背后的分子机制，我们发现APP以时间依赖性和饱和性方式与蛋白聚糖的糖胺聚糖侧链结合，但不与硫酸软骨素结合。我们还证明了APP碳水化合物结构域内的高亲和力肝素结合位点与APP的锌（II）结合位点之间存在相互作用。我们发现，在微摩尔浓度的锌（II）存在下，对肝素的亲和力增加了两到四倍。因此，微摩尔浓度的锌（II）似乎能够调节APP与蛋白聚糖肝素侧链的结合，并且如先前所示[《科学》265（1994）1464 - 1467]，能够诱导可溶性淀粉样β A4蛋白的聚集。
