INTERACTION BETWEEN THE ZINC(II) AND THE HEPARIN-BINDING SITE OF THE ALZHEIMERS-DISEASE BETA-A4 AMYLOID PRECURSOR PROTEIN (APP)

被引:84
作者
MULTHAUP, G [1 ]
BUSH, AI [1 ]
POLLWEIN, P [1 ]
MASTERS, CL [1 ]
机构
[1] UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA
关键词
ALZHEIMERS DISEASE; HEPARIN BINDING; ZINC BINDING; BETA-A4; AMYLOID;
D O I
10.1016/0014-5793(94)01176-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:151 / 154
页数:4
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